Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

Refractory Follicular Lymphoma Clinical Trial

Official title:

Randomized Phase II Trial in Early Relapsing or Refractory Follicular Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03269669
• Other study ID #: NCI-2017-00009
• Secondary ID: NCI-2017-00009S1
• Status: Recruiting
• Phase: Phase 2
• Start date: January 23, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.

Description:

PRIMARY OBJECTIVE:

I. To compare the complete response rate up to 6 cycles after randomization as defined by centrally read positron emission tomography (PET)/computed tomography (CT) (integral biomarker) of 2 targeted therapeutic regimens (obinutuzumab + umbralisib [TGR-1202] or obinutuzumab + lenalidomide) with obinutuzumab + chemotherapy (cyclophosphamide, doxorubicin hydrochloride [doxorubicin], vincristine sulfate [vincristine], and prednisone [CHOP] or bendamustine hydrochloride [bendamustine]) in patients with early relapsing or refractory follicular lymphoma.

SECONDARY OBJECTIVES:

I. To validate the prognostic association of the m7-FLIPI model, demonstrating that the population of follicular lymphoma patients who respond poorly to chemoimmunotherapy are enriched for having a high-risk m7-FLIPI score, and that the score is associated with progression-free survival (integrated biomarker). (Primary translational medicine) II. To estimate the 30-month sustained complete response rate (CR30) defined by centrally read PET/CT with each of the regimens in this early relapsing or refractory follicular lymphoma population.

III. To estimate best response up to 12 cycles of therapy, progression free survival, duration of response and overall survival with each of the combinations in early relapsing or refractory follicular lymphoma.

IV. To evaluate the adverse effects of each of the regimens in early relapsing or refractory follicular lymphoma.

V. To evaluate the predictive performance of non-invasive genotyping (m7-FLIPI in circulating tumor deoxyribonucleic acid [DNA]) of plasma at study entry relative to standard tumor genotyping (m7-FLIPI) of formalin-fixed paraffin-embedded tumor tissue.

VI. To evaluate the association between the detection of active lymphoma by PET-CT and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I (CLOSED TO ACCRUAL): Patients receive obinutuzumab intravenously (IV) on day 1 and umbralisib orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM III:

PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity.

Patients in all arms undergo biopsy and echocardiogram (ECHO) or multigated acquisition scan (MUGA) during screening, and PET/CT scans and collection of blood throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on PET/CT; patients that have involvement with large cell lymphoma are not eligible

• Patients must have a whole body or limited whole body PET/CT scan performed within 42 days prior to registration

• Patients must have bone marrow biopsy performed within 42 days prior to registration

• Patients must have an indication for therapy as determined by the treating investigator

• All disease must be assessed and documented on the S1608 FDG-PET/CT assessment form

• The intent is to enroll patients with follicular lymphoma (FL) relapsed within 2 years of completing their first course of chemotherapy (CHOP or bendamustine based therapy) + anti-CD20 therapy. Patient is still eligible if he/she received radiation therapy or anti-CD20 therapy prior to chemoimmunotherapy or if maintenance anti-CD20 therapy was administered after chemoimmunotherapy

• Patients must have either failed to achieve a complete remission, or must have relapsed within 2 years after completing CHOP or bendamustine-containing chemoimmunotherapy (including an anti-CD20 monoclonal antibody), as measured from the last dose of CHOP or bendamustine; relapsed patients must not have received any intervening chemotherapy

• Patients must have received only 1 course of chemotherapy, containing at least 3 cycles of CHOP or bendamustine; (note that no minimum dose of bendamustine is required)

• Patients who received any anti-CD20 antibody therapy prior to CHOP or bendamustine are eligible

• Patients who additionally received any maintenance anti-CD-20 antibody therapy or consolidative radioimmunotherapy within 2 years of the last dose of the CHOP or bendamustine therapy are eligible

• Involved field or involved site radiation is not considered a line of therapy; examples of eligible prior treatment regimens (note this list is not all inclusive):

• 1st line rituximab treatment followed years later by bendamustine rituximab

• Bendamustine rituximab x 4 cycles

• 1st line rituximab treatment, 2nd line ibritumomab tiuxetan, followed by bendamustine bortezomib rituximab x 6 cycles followed by rituximab maintenance

• Bendamustine obinutuzumab x 3 cycles

• CHOP rituximab x 6 cycles followed by rituximab maintenance

• For all forms of systemic therapy, patients must have completed therapy at least 21 days prior to registration; patients must have completed any radioimmunotherapy at least 84 days prior to registration; patients prior treatment related toxicities (except alopecia) must have resolved to grade 1 or less prior to registration

• Patients must have tissue specimens collected prior to registration; patients must be offered participation in biobanking of residual specimens; with patient consent, residuals from the mandatory submission(s) will be banked for future research

• Patients must be >= 18 years of age

• All patients must have a Zubrod performance status of 0, 1 or 2

• Absolute neutrophil count (ANC) >= 1,500/mcL within 28 days prior to registration

• Platelets >= 75,000/mcL within 28 days prior to registration

• Patients must have adequate renal function as documented by a calculated creatinine clearance >= 60 mL/min, within 28 days prior to registration

• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (=< 5 x IULN if secondary to lymphoma, Gilbert's syndrome, or medication related [e.g., indinavir, tenofovir, atazanavir]) within 28 days prior to registration

• Direct bilirubin =< 1.5 x IULN (=< 5 x IULN if secondary to lymphoma) within 28 days prior to registration

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (=< 5 x IULN secondary to lymphoma) within 28 days prior to registration

• Patients must have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 42 days prior to registration with a cardiac ejection fraction >= 45%

• Patients with hepatitis B virus infection must have undetectable hepatitis B virus (HBV) on suppressive therapy and no evidence of HBV-related hepatic damage; patients with hepatitis C virus infection are eligible if complete eradication therapy has been successfully completed, and there is no detectable hepatitis C virus (HVC) or related hepatic damage; patients with known human immunodeficiency virus (HIV) infection are eligible if they meet all of the following criteria in addition to the other protocol eligibility criteria:

• Patient must have no history of acquired immune deficiency syndrome (AIDS)-related complications, other than a history of low CD4+ T-cell count (< 200/mm^3) prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to leukemia and should not be used as an exclusion criterion if low

• Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the leukemia

• Patient must have serum HIV viral load of < 200 copies/mm^3

• Patient must be on combination antiretroviral therapy with minimal pharmacokinetic interactions with study therapy and minimal overlapping clinical toxicity with protocol therapy; (recommend a regimen of the integrase inhibitor dolutegravir combined with either disoproxil fumarate/emtricitabine or dolutegravir combined with tenofovir alafenamide/emtricitabine)

• Protease inhibitors and once daily formulations containing cobicistat are NOT allowed due to potential pharmacokinetic interactions with leukemia therapy

• Stavudine and zidovudine (AZT) are NOT allowed because of overlapping toxicity with protocol therapy

• Patients must be able and willing to receive prophylaxis with daily aspirin, low molecular weight heparin, factor X inhibitors or warfarin if randomized to lenalidomide; patients unable or unwilling to take any listed prophylaxis are NOT eligible

• No second prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for three years

• Patients must have a complete history and physical examination within 28 days prior to registration

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to complete abstinence (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence [e.g., calendar, ovulation, symptothermal or post ovulation methods] and withdrawal are not acceptable methods of contraception) from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; while taking lenalidomide, during dose interruptions, and for at least 28 days after the last dose of lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a female who: 1) has achieved menarche at some point; 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; NOTE: patients not randomized to receive lenalidomide will not be required to undergo serial pregnancy testing or lenalidomide counseling after registration

• Patients must have lactate dehydrogenase (LDH) and beta-2-microglobulin collected within 28 days prior to registration

• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Exclusion Criteria:

• Patients must not have clinical evidence of central nervous system involvement by lymphoma since the proposed treatment strategies are not designed to address central nervous system (CNS) involvement adequately; if performed, any laboratory or radiographic tests performed to assess CNS involvement must be negative

• Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide

Related Conditions & MeSH terms

• Grade 1 Follicular Lymphoma
• Grade 2 Follicular Lymphoma
• Grade 3a Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular
• Recurrent Follicular Lymphoma
• Refractory Follicular Lymphoma

Intervention

Drug:
• Bendamustine Hydrochloride
Given IV

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo collection of blood
• Computed Tomography
Undergo PET/CT scans

Drug:
• Cyclophosphamide
Given IV
• Doxorubicin Hydrochloride
Given IV

Procedure:
• Echocardiography
Undergo ECHO

Drug:
• Lenalidomide
Given PO

Procedure:
• Multigated Acquisition Scan
Undergo MUGA

Biological:
• Obinutuzumab
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET/CT scans

Drug:
• Prednisone
Given PO
• Umbralisib
Given PO
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	PCR Oncology	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Hematology/Oncology Clinic PLLC	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Trinity Health Medical Center - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Chelsea Hospital	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Main Line Health Center-Collegeville	Collegeville	Pennsylvania
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Denver Health Medical Center	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Kaiser Permanente Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Main Line Health Center-Exton	Exton	Pennsylvania
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	City of Hope Seacliff	Huntington Beach	California
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	City of Hope at Irvine Lennar	Irvine	California
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Marshfield Medical Center - Ladysmith	Ladysmith	Wisconsin
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	City of Hope at Long Beach Elm	Long Beach	California
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Licking Memorial Hospital	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	City of Hope Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Kaiser Permanente-Ontario	Ontario	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	UW Health Carbone Cancer Center Rockford	Rockford	Illinois
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Corewell Health Lakeland Hospitals - Saint Joseph Hospital	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	City of Hope South Bay	Torrance	California
United States	Munson Medical Center	Traverse City	Michigan
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR)		Up to 6 cycles
Secondary	Sustained complete response rate (CR30)	Defined by centrally read positron emission tomography (PET)/computed tomography (CT).	Up to 30 months
Secondary	Progression-free survival (PFS)	Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 31 eligible patients in each arm, progression free survival at a particular time point, and the 30-month sustained response rate can be estimated to within at least +/- 18% with 95% confidence.	From date of registration to date of first observation of progressive disease, or death due to any cause, assessed up to 5 years
Secondary	Duration of response (CR, partial response [PR])	Will be calculated using the method of Kaplan-Meier.	From date of first documentation of response to treatment (CR, PR) to date of first documentation of progression, or death due to any cause, assessed up to 5 years
Secondary	Overall survival (OS)	Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 31 eligible patients in each arm, OS at a particular time point, and the 30-month sustained response rate can be estimated to within at least +/- 18% with 95% confidence.	Up to 5 years
Secondary	Incidence of adverse events	Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (version 5.0 will be utilized for serious adverse events reporting only). Toxicity rates can be estimated to within at least +/- 18% with 95% confidence.	Up to 5 years
Secondary	Non-invasive genotyping and circulating tumor deoxyribonucleic acid (DNA) assessment	Sensitivity, specificity, positive predictive value, negative predictive value, and kappa coefficient will be used to evaluate the concordance. Will evaluate the association of detection of active lymphoma by positron emission tomography-computed tomography and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy. Chi-square test will be used to evaluate the association and odds ratio will be calculated	Up to 5 years
Secondary	Active lymphoma and circulating tumor DNA in plasma	The Cox proportional hazards model will be used to assess the association and odds ratio will be calculated.	From baseline up to 30 months after initiation of treatment
Secondary	m7-FLIPI model validation	The Cox proportional hazards model will be used to assess the association of the m7-FLIPI with to PFS.	Up to 5 years