Pembrolizumab and Dasatinib, Imatinib Mesylate, or Nilotinib in Treating Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease

Minimal Residual Disease Clinical Trial

Official title:

Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03516279
• Other study ID #: EA9171
• Secondary ID: NCI-2017-02161EA
• Status: Recruiting
• Phase: Phase 2
• Start date: June 26, 2019
• Est. completion date: August 31, 2031

Study information

• Verified date: November 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well pembrolizumab and dasatinib, imatinib mesylate, or nilotinib work in treating patients with chronic myeloid leukemia and persistent detection of minimal residual disease, defined as the levels of a gene product called bcr-abl in the blood. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Dasatinib, imatinib mesylate, and nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and dasatinib, imatinib mesylate, or nilotinib may work better in treating patients with chronic myeloid leukemia.

Description:

PRIMARY OBJECTIVES:

I. Assess the proportion of chronic myelogenous leukemia (CML) patients on stable-dose tyrosine kinase inhibitor (TKI) who convert to undetectable minimal residual disease (UMRD) (molecular response [MR]^4.5) during or within 2 years of initiating pembrolizumab therapy.

SECONDARY OBJECTIVES:

I. Among patients who have converted to UMRD (MR^4.5), assess the proportion of CML patients who maintain UMRD for 6 months and 12 months.

II. Among patients who have converted to UMRD (MR^4.5), assess the proportion of CML patients who discontinue their TKI.

III. Among patients who have converted to UMRD (MR^4.5), assess the proportion of CML patients who are UMRD and TKI-free at 2 years from first determined UMRD.

IV. Assess the proportion of CML patients who develop grade 3 or 4 immune related adverse events related to pembrolizumab treatment during the first 2 years after registration (not including grade 3 events that respond to corticosteroids and improve to grade 1 or less within 4 weeks).

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and dasatinib, imatinib mesylate, or nilotinib orally (PO) as clinically indicated per the treating physician. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients with detectable MRD after course 18 continue pembrolizumab and dasatinib, imatinib mesylate, or nilotinib every 21 days for up to an additional 18 courses in the absence of disease progression or unacceptable toxicity. Patients with UMRD at any time before course 18 discontinue pembrolizumab after course 18 and continue dasatinib, imatinib mesylate, or nilotinib every 21 days for up to an additional 18 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 6 years from the date of registration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 31, 2031
• Est. primary completion date: August 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• PREREGISTRATION (STEP 0): Patient has pathologically-confirmed chronic phase-CML on a first line TKI and must meet the following criteria:

• The patient has to be on first-line TKI therapy (the same TKI) for at least 2 years prior to pre-registration

• Has been in MMR (i.e. MR^3) but still have detectable BCR-ABL transcript by a standard real-time quantitative polymerase chain reaction (RQ-PCR) assay with a limit of detection (sensitivity) of 4.5 for at least 12 months from the first documentation of the MMR

• Patient has not achieved MR^4.5 (complete molecular remission [CMR]) within the time of initiation of TKI therapy and pre-registration

• PREREGISTRATION (STEP 0): Patient must be scheduled to undergo a standard of care bone marrow biopsy within 7 days of step 0 registration

• PREREGISTRATION (STEP 0): Peripheral blood must be collected for submission to Fred Hutchinson Cancer Research Center for central assessment of the establishment of BCR/ABL status to confirm patient?s eligibility for registration to Step 1; Fred Hutchinson will forward results within 1-2 business days of receipt of the peripheral blood to the submitting institution

• REGISTRATION TO TREATMENT (STEP 1): Institution has received central BCR-ABL test results confirming MRD positive status

• REGISTRATION TO TREATMENT (STEP 1): Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• REGISTRATION TO TREATMENT (STEP 1): No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation

• REGISTRATION TO TREATMENT (STEP 1): No current use of corticosteroids; EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted

• REGISTRATION TO TREATMENT (STEP 1): No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =< 2 years

• NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer)

• REGISTRATION TO TREATMENT (STEP 1): Women must not be pregnant or breastfeeding; patients must also not expect to conceive or father children from the time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment; all females of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of pembrolizumab; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• REGISTRATION TO TREATMENT (STEP 1): Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or to abstain from sexual from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment

• REGISTRATION TO TREATMENT (STEP 1): Patients must have been on a stable dose of the TKI for the last 3 months prior to pre-registration

• REGISTRATION TO TREATMENT (STEP 1): Patient may not be currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have a known history of active TB (Bacillus Tuberculosis)

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have a history of hypersensitivity to pembrolizumab or any of its excipients

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have received a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study registration or have not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have had prior chemotherapy, targeted small molecule therapy (aside from imatinib, dasatinib, or nilotinib), or radiation therapy within 2 weeks prior to study registration; patients also must have recovered from all adverse events due to a previously administered agent

• Note: Patients with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study

• REGISTRATION TO TREATMENT (STEP 1): Patients who have received major surgery must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of protocol treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to protocol treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have known history of, or any evidence of active, non-infectious pneumonitis

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have an active infection requiring systemic therapy

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

• REGISTRATION TO TREATMENT (STEP 1): Patients who are Human Immunodeficiency Virus (HIV) positive are eligible if they have undetectable HIV viral load and CD4+ T-cell count = 250/mm3.

• REGISTRATION TO TREATMENT (STEP 1): Patients with a known positive test for Hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection might be enrolled if the viral load by PCR is undetectable with/without active treatment.

• REGISTRATION TO TREATMENT (STEP 1): Patients must not have known history of hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive).

• REGISTRATION TO TREATMENT (STEP 1): Patient must not have received a live vaccine within 30 days of planned start of study therapy

• NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

• REGISTRATION TO TREATMENT (STEP 1): Absolute neutrophil count (ANC) >= 1,500 /mcL, within 14 days prior to first dose of pembrolizumab

• REGISTRATION TO TREATMENT (STEP 1): Platelet count >= 100,000 /mcL, within 14 days prior to first dose of pembrolizumab

• REGISTRATION TO TREATMENT (STEP 1): Hemoglobin (Hgb) >= 9 g/dL OR >= 5.6 mmol/L without transfusion of erythropoietin (EPO) dependency, within 14 days prior to first dose of pembrolizumab

• REGISTRATION TO TREATMENT (STEP 1): Serum creatinine =< 1.5 X upper limit of normal (ULN) OR creatinine clearance (per institutional standards) >= 60 mL/min for patient with creatinine levels > 1.5 X ULN, within 14 days prior to first dose of pembrolizumab

• REGISTRATION TO TREATMENT (STEP 1): Serum total bilirubin =< 1.5 X ULN OR direct bilirubin

=< ULN for subjects with total bilirubin levels > 1.5 X ULN, within 14 days prior to first dose of pembrolizumab

• REGISTRATION TO TREATMENT (STEP 1): Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases, within 14 days prior to first dose of pembrolizumab

• REGISTRATION TO TREATMENT (STEP 1): Patients should not be receiving concomitant strong CYP3A4 inducers or inhibitors = 7 days prior to registration due to their potential to effect the activity or pharmacokinetics of study agents and/or QT interval prolongation toxicity. Should treatment with any of these agents be required, consult with study chair.

• REGISTRATION TO TREATMENT (STEP 1): Patients should not have received prior allogeneic transplant.

Related Conditions & MeSH terms

• Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Minimal Residual Disease
• Neoplasm, Residual

Intervention

Drug:
• Dasatinib
Given PO
• Imatinib Mesylate
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Nilotinib
Given PO

Biological:
• Pembrolizumab
Given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center	Adrian	Michigan
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
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	MetroHealth Medical Center	Cleveland	Ohio
United States	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
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	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System Eau Claire Hospital-Luther Campus	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Saint Francis Hospital	Federal Way	Washington
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	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	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Smilow Cancer Hospital Care Center - Guiford	Guilford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	Jewish Hospital	Louisville	Kentucky
United States	Jewish Hospital Medical Center Northeast	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Garnet Health Medical Center	Middletown	New York
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
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	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Community Medical Center	Scranton	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
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	Geisinger Medical Group	State College	Pennsylvania
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Mercy Hospital Washington	Washington	Missouri
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
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	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients on tyrosine kinase inhibitor (TKI) who convert to undetectable minimal residual disease (UMRD)	Will be reported with exact confidence intervals. The binomial test will be used to test the null hypothesis that this proportion is 0.2 with the alternative hypothesis being that this proportion is greater than 0.2.	Up to 2 years of initiating pembrolizumab
Secondary	Proportion of patients who maintain UMRD for 6 months	Will be assessed among patients who achieve UMRD within two years of initiating pembrolizumab. The proportions will be reported with exact confidence intervals.	Up to 6 years
Secondary	Proportion of patients who maintain UMRD for 6 and 12 months	Will be assessed among patients who achieve UMRD within two years of initiating pembrolizumab. The proportions will be reported with exact confidence intervals.	Up to 6 years
Secondary	Proportion of patients who meet the criteria for discontinuing TKI	Will be assessed among patients who achieve and maintain UMRD within two years of initiating pembrolizumab. The proportions will be reported with exact confidence intervals.	Up to 6 years
Secondary	Proportion of patients who maintain UMRD for 2 years after first achieving UMRD	Will be assessed among patients who have converted to UMRD (molecular response [MR]^4.5) and discontinued TKI. The proportions will be reported with exact confidence intervals.	Up to 6 years
Secondary	Proportion of patients who develop grade 3 or 4 immune related adverse events (not including grade 3 events that respond to corticosteroids and improve to grade 1 or less within 4 weeks)	Will be tabulated based on grade Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 6 years