Testing Nivolumab to Prevent Disease From Coming Back After Treatment in Patients With Acute Myeloid Leukemia, REMAIN Trial

NCT ID: NCT02275533

Last Updated: 2025-12-08

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-02

Study Completion Date

2026-10-08

Brief Summary

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This phase II trial studies how well nivolumab works in eliminating any remaining cancer cells and preventing cancer from returning in patients with acute myeloid leukemia that had a decrease in or disappearance of signs and symptoms of cancer after receiving chemotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate and compare the progression free survival rate after randomization in the two treatment arms (nivolumab versus \[vs.\] observation).

SECONDARY OBJECTIVES:

I. To determine and compare the overall survival rates in the two arms. II. To determine and compare the incidence of non-relapse mortality in the two arms.

III. To evaluate the toxicities of nivolumab as maintenance.

EXPLORATORY OBJECTIVES:

I. To analyze PD-L1 expression on acute myeloid leukemia (AML) cells from peripheral blood and/or bone marrow samples at diagnosis if available and at the time of study enrollment.

II. To monitor AML minimal residual disease (MRD) by Wilms tumor 1 (WT1) polymerase chain reaction (PCR) at enrollment and at subsequent defined time points in the nivolumab-treated and control groups.

III. To perform an exploratory analysis on the frequencies, absolute numbers and subsets of T cells (including regulatory T cells) in the nivolumab-treated and control groups with an emphasis on activation markers.

IV. To perform deep sequencing of T cell receptor (TCR)-alpha and TCR-beta chains on polyclonal T cells at baseline and at subsequent time points in the nivolumab and control groups.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy at screening, months 3, 6, and 12, as clinically indicated, and at the time off study. Patients also undergo collection of blood samples at screening, weeks 9, 13, 25, and 53, and during off-study evaluation or at time of clinically suspected relapse. Patients may undergo echocardiography (ECHO) as clinically indicated.

ARM II: Patients undergo standard of care clinical observation for up to 2 years. Upon disease relapse, patients may cross-over to Arm I. Patients also undergo bone marrow biopsy at screening, months 3, 6, and 12, as clinically indicated, and during off-study evaluation. Patients also undergo collection of blood samples at screening, weeks 9, 13, 25, and 53, and during off-study evaluation or at time of clinically suspected relapse. Patients may undergo ECHO as clinically indicated.

After completion of study treatment, patients are followed up periodically for 2 years, every 6 months for 1 year, and then yearly thereafter.

Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (nivolumab)

Patients receive nivolumab IV over 60 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy at screening, months 3, 6, and 12, as clinically indicated, and during off-study evaluation. Patients also undergo collection of blood samples at screening, weeks 9, 13, 25, and 53, and during off-study evaluation or at time of clinically suspected relapse. Patients may undergo ECHO as clinically indicated.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Arm II (observation)

Patients undergo standard of care clinical observation for up to 2 years. Upon disease relapse, patients may cross-over to Arm I. Patients also undergo bone marrow biopsy at screening, months 3, 6, and 12, as clinically indicated, and during off-study evaluation. Patients also undergo collection of blood samples at screening, weeks 9, 13, 25, and 53, and during off-study evaluation or at time of clinically suspected relapse. Patients may undergo ECHO as clinically indicated.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Clinical Observation

Intervention Type OTHER

Undergo standard of care clinical observation

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Interventions

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Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Clinical Observation

Undergo standard of care clinical observation

Intervention Type OTHER

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow Biopsy, Bone Marrow observation EC Echocardiography ABP 206 BCD-263 BMS 936558 BMS-936558 BMS936558 CMAB819 MDX 1106 MDX-1106 MDX1106 NIVO Nivolumab Biosimilar ABP 206 Nivolumab Biosimilar BCD-263 Nivolumab Biosimilar CMAB819 ONO 4538 ONO-4538 ONO4538 Opdivo

Eligibility Criteria

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Inclusion Criteria

* AML patients in first complete remission (CR) (CR1) or first complete remission with incomplete blood count recovery (CRi) after induction and/or consolidation chemotherapy; except young (\< 60 years) AML patients in European LeukemiaNet favorable group; (Since young AML patients in the European LeukemiaNet favorable group have excellent 2 year progression free survival \[PFS\] at around 64%, further maintenance therapy might not provide additional benefit; thus the current trial will exclude young favorable group AML patients), patients could receive any cycle consolidation or no consolidation per the discretion by the treating physician
* Within 60 days after bone marrow biopsy confirmed remission after the patients recover from their last course of chemotherapy, the goal to consent the eligible patient prior to the remission confirmation bone marrow biopsy at the end of the planned chemotherapy); ideally, the research samples will be collected during the bone marrow biopsy, and the patient will be enrolled to the study within 2 weeks of the bone marrow biopsy; if there is delay to enroll the patient after the bone marrow biopsy and research sample collection, it is ok not to repeat bone marrow biopsy within 4 weeks, after the last bone marrow biopsy, if there is no sign of disease relapse; a repeat bone marrow biopsy should be done if the delay of enrollment is more than 4 weeks after the last bone marrow biopsy; patients with confirmed remission within 60 days after the last bone marrow biopsy, without research samples collection, should have a repeat bone marrow biopsy conducted within two weeks prior to enrolling on the study
* Patient is not a candidate for stem cell transplant due to advanced age or co-morbidities; or the enrollee does not have donor available; or the enrollee declines stem cell transplant due to personal belief; or stem cell transplant is not standard of care based on the risk category of disease
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
* Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status of 0 or 1 (Karnofsky \>= 70%)
* Life expectancy of greater than 6 months
* Leukocytes \>= 1,500/mcL
* Absolute neutrophil count \>= 1,000/mcL
* Platelets \>= 50,000/mcL or recovery to the baseline count
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN
* Amylase and lipase =\< 1.5 x ULN without any symptoms of pancreatitis
* Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula)
* The effects of nivolumab on the developing human fetus are unknown; for this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug nivolumab; women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab; women must not be breastfeeding; men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception
* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
* WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; these durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
* Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier
* Patients who are receiving any other investigational agents
* Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
* Patients with known central nervous system (CNS) involvement may be excluded because of poor prognosis and concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; however, if CNS disease is cleared before the treatment with nivolumab, patients could be allowed if no permanent CNS damage
* History of severe hypersensitivity reaction to any monoclonal antibody
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because nivolumab is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab
* Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) might be enrolled if the viral load by PCR is undetectable with/without active treatment and absolute lymphocyte count \>= 350/ul
* Patients with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (hepatitis C virus \[HCV\] antibody) indicating acute or chronic infection might be enrolled if the viral load by PCR is undetectable with/without active treatment
* Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =\< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =\< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
* Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wendy Stock

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center EDDOP

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Los Angeles General Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Moffitt Cancer Center-International Plaza

Tampa, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

Site Status

University of Chicago Medicine-Orland Park

Orland Park, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Clinical Research Center

Fairway, Kansas, United States

Site Status

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

NCI - Center for Cancer Research

Bethesda, Maryland, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Site Status

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Ben Taub General Hospital

Houston, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Pyzer AR, Dillon LW, Sharon E, Karrison TG, Zha Y, Fulton N, Gui G, Andrew G, Streicher H, Sweet K, Yaghmour G, Liu JJ, Jonas BA, Schimmer AD, Grant S, Zeidan AM, Hildebrandt GC, Lowrey CH, Mattison RJ, Palmisiano N, Salhotra A, Tzachanis D, Baer MR, Lin TL, Patel P, Chen H, Stadler WM, Odenike O, Larson RA, Gajewski TF, Hourigan CS, Stock W, Liu H. Randomized phase 2 study to assess the role of single-agent nivolumab to maintain remission in acute myeloid leukemia. Blood Adv. 2025 May 13;9(9):2144-2152. doi: 10.1182/bloodadvances.2024015176.

Reference Type DERIVED
PMID: 39928953 (View on PubMed)

Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

Reference Type DERIVED
PMID: 33394722 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2014-02167

Identifier Type: REGISTRY

Identifier Source: secondary_id

CIRB 15-0185

Identifier Type: -

Identifier Source: secondary_id

CVCIRB 15-0185

Identifier Type: -

Identifier Source: secondary_id

9706

Identifier Type: OTHER

Identifier Source: secondary_id

9706

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186644

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186686

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186689

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186691

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186712

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186717

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ZIABC011078

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2014-02167

Identifier Type: -

Identifier Source: org_study_id

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