S1106 Rituximab With Combination Chemotherapy or Bendamustine Hydrochloride Followed by Consolidation Chemotherapy and Stem Cell Transplantation in Older Patients With Previously Untreated Mantle Cell Lymphoma

Lymphoma Clinical Trial

Official title:

A Randomized Phase II Trial of R-HCVAD/MTX/ARA-C Induction Followed by Consolidation With an Autologous Stem Cell Transplant Vs. R-Bendamustine Induction Followed by Consolidation With an Autologous Stem Cell Transplant for Patients ≤ 65 Years of Age With Previously Untreated Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01412879
• Other study ID #: CDR0000707601
• Secondary ID: S1106U10CA032102
• Status: Completed
• Phase: Phase 2
• Start date: November 2011
• Est. completion date: March 2021

Study information

• Verified date: October 2021
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy also work in different ways to kill more cancer cells or stop them from growing. It is not yet known whether rituximab is more effective with combination chemotherapy or bendamustine hydrochloride in treating patients with mantle cell lymphoma undergoing peripheral blood stem cell transplantation.

PURPOSE: This randomized phase II trial studies how well giving rituximab together with combination chemotherapy or bendamustine hydrochloride followed by consolidation chemotherapy and peripheral blood stem cell transplantation works in treating older patients with previously untreated mantle cell lymphoma.

Description:

OBJECTIVES:

• To estimate the 2-year progression-free survival (PFS) of patients with newly diagnosed mantle cell lymphoma (MCL) treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone (RHCVAD), methotrexate and cytarabine (MTX/Ara-C), and autologous stem cell transplant (ASCT) or rituximab and bendamustine (R-bendamustine) and autologous stem cell transplant and to select a regimen for further development.

• To assess the response rate and overall survival of patients with newly diagnosed MCL treated with R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT.

• To assess the toxicity and tolerability of R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT in patients with newly diagnosed MCL.

• To determine the prognostic value of quantitative minimal-residual disease (MRD) monitoring in the peripheral blood of MCL patients after induction therapy and serially after high-dose chemotherapy and ASCT on treatment outcome.

• To bank diagnostic tissue sections for future translational research studies.

OUTLINE: This is a multicenter study. Patients are stratified according to risk classification by Mantle Cell Lymphoma International prognostic Index (MIPI) score (low risk vs intermediate/high risk). Patients are randomized to 1 of 2 treatment arms.

• Arm I (induction therapy):

• Courses 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2.

• Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of course 2.

• Each course is 21 days long and continues in the absence of disease progression or unacceptable toxicity.

• Arm II (induction therapy):

• Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks later, patients with responsive disease receive 2 additional courses of treatment.

• Stem cell mobilization: Beginning within 8 weeks, patients receive rituximab IV and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell collection about 26 days later.

Consolidation therapy: Patients receive one of the following preparative regimens.

• BCV* chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2.

• BEAM* chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1.

• TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2.

• NOTE: * Patients 61 years of age or older receive either BCV or BEAM.

• NOTE: * *TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 8 years from registration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: March 2021
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

• All patients must have previously untreated stage III, IV, or bulky stage II mantle cell lymphoma (MCL)

• A diagnosis of MCL must be confirmed by histopathological diagnosis including immunohistochemistry and flow cytometry documenting both of the following phenotypes:

• CD19+ or CD20+

• Cyclin D1+ or evidence of the t(11;14) translocation by cytogenetics or FISH

• Adequate sections from the original diagnostic specimen must be available for submission for central review

• An adequate biopsy requires sufficient tissue to establish the architecture and a WHO histologic subtype with certainty

• Core biopsies, especially multiple core biopsies, MAY be adequate, but needle aspirations or cytologies are not adequate

• Bone marrow core biopsy or clot sections (not aspirates) may be used as diagnostic material if it is significantly involved and are the only diagnostic material available

• All patients must have bidimensional measurable disease documented on the Lymphoma Baseline Tumor Assessment Form (Form #48031)

• Patients who also have non-measurable disease in addition to measurable disease must have all nonmeasurable disease assessed within 28 days prior to registration

• Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma

• Any laboratory or radiographic tests performed prior to registration to assess CNS involvement must be negative

• Patients must have a unilateral/bilateral bone marrow aspirate and biopsy for staging performed within 42 days prior to registration

• If the biopsy cannot be performed but the aspirate is unequivocally consistent with mantle cell lymphoma, this will be considered adequate for staging purposes

• Patients must be eligible for stem cell transplantation by institutional guidelines with the plan that transplant will be conducted at a cooperative group-approved transplant center

• Patients must be planning to undergo stem cell transplantation within 84 days after day 1 of the last induction course

• Patients must have had at least 1.5 X 10^6 CD34^+ cells/kg collected and stored prior to second registration for stem cell transplantation

PATIENT CHARACTERISTICS:

• Zubrod performance status of 0-2

• Bilirubin = 3 times upper limit of normal (ULN)

• Serum creatinine = 2.0 times ULN

• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) = 2.5 times ULN

• Alkaline phosphatase = 2.5 times ULN

• Platelet count = 100,000/mcL, unless due to bone marrow infiltration by lymphoma

• All patients = 45 years of age must have an echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA )scan within 42 days prior to registration (whichever method is used at baseline must be used at restaging)

• Patients < 45 years of age should have ECHO/MUGA only if clinically indicated

• Patients with an ejection fraction < institutional lower limit of normal (ILLN) are not eligible

• Serum Lactate dehydrogenase (LDH) and a Complete Blood Count (CBC with differential must be measured within 28 days prior to registration

• Patients known to be HIV positive, or who have a history of solid organ transplantation, are ineligible

• No active hepatitis

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated Stage I or II cancer from which the patient is currently in complete remission; or any other cancer from which the patient has been disease-free for 5 years

• Pregnant or nursing women may not participate

• Women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Biological:
• rituximab
Given IV

Drug:
• bendamustine hydrochloride
Given IV
• cyclophosphamide
Given IV
• cytarabine
Given IV
• dexamethasone
Given PO or IV
• doxorubicin hydrochloride
Given IV
• leucovorin calcium
Given PO or IV
• methotrexate
Given IV
• vincristine sulfate
Given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McFarland Clinic, PC	Ames	Iowa
United States	Island Hospital Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Overlake Cancer Center at Overlake Hospital Medical Center	Bellevue	Washington
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Highline Medical Center Cancer Center	Burien	Washington
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Providence Centralia Hospital	Centralia	Washington
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Baylor University Medical Center - Dallas	Dallas	Texas
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	Illinois CancerCare - Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	St. Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Illinois CancerCare - Galesburg	Galesburg	Illinois
United States	North Colorado Medical Center	Greeley	Colorado
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Hospital Cancer Center	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina
United States	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey
United States	Illinois CancerCare - Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Swedish Medical Center - Issaquah Campus	Issaquah	Washington
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	St. Joseph Regional Medical Center	Lewiston	Idaho
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	McDonough District Hospital	Macomb	Illinois
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Willamette Falls Hospital	Oregon City	Oregon
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	Illinois CancerCare - Spring Valley	Spring Valley	Illinois
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Allenmore Hospital	Tacoma	Washington
United States	CCOP - Northwest	Tacoma	Washington
United States	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	St. Clare Hospital	Tacoma	Washington
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) at 2 Years	Disease progression is defined using the 2007 revised Cheson et al. criteria that is at least 50% increase in sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed, or >= 50% increase in greatest transverse diameter (GTD) of any nodal > 1 cm in shortest axis, or >= 50% increase in the SPD of other target measurable lesions over the smallest sum observed, any new bone marrow involvement, any new lesion, lymph node with long axis is > 1.5 cm or if both long and short axes are > 1 cm, PET positive if patients with no pretreatment PET scan or when PET scan was positive before therapy. Progression-free survival is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.	Up to 2 years
Secondary	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	Up to 8 months (Assessed at the beginning of each cycle of treatment, at restaging, and at post transplant.)
Secondary	Response Rate (Complete and Partial Response)	Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.	Up to 9 months
Secondary	5-year Overall Survival (OS)	Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.	Up to 5 years