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Nivolumab in Eliminating Minimal Residual Disease and Preventing Relapse in Patients With Acute Myeloid Leukemia in Remission After Chemotherapy

This study is currently recruiting participants.
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Verified May 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02275533
First received: October 24, 2014
Last updated: July 19, 2017
Last verified: May 2017
October 24, 2014
July 19, 2017
May 27, 2015
June 28, 2019   (Final data collection date for primary outcome measure)
Progression free survival (PFS) [ Time Frame: Time from randomization to disease relapse or death from any cause, assessed up to 2 years post-treatment ]
Kaplan-Meier plots will be used to estimate PFS in each arm and a stratified log rank test will be performed to compare the two groups. In addition, Cox proportional hazards models will be fit to provide estimates of the hazard ratio (HR) and associated 95% confidence interval (CIs), both unadjusted and adjusted for baseline covariates. Descriptive, subset analysis of PFS will be performed for MRD positive patients.
Same as current
Complete list of historical versions of study NCT02275533 on ClinicalTrials.gov Archive Site
  • Incidence of adverse effects of nivolumab assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 100 days post-treatment ]
    Summary tables for AEs will include only AEs that started or worsened after randomization. The incidence of treatment-related adverse events (new or worsening from baseline after randomization) will be summarized by system organ class and/ or preferred term, severity (based on CTCAE grades), type of adverse event, and relation to study treatment by treatment group. Toxicity rates will be compared between the two treatment arms via chi-squares or Fisher's exact tests.
  • Non-relapse mortality (NRM) [ Time Frame: Duration between the date of randomization and the date of patient death due to reasons other than relapse, assessed up to 2 years post-treatment ]
    NRM will be analyzed using competing risks models with deaths due to relapse as a competing risk. Cumulative incidence curves will be generated and treatment effects summarized using the sub-distribution hazard ratio with and without adjustment for covariates
  • Overall survival (OS) [ Time Frame: Time from randomization to the date of death from any cause, assessed up to 2 years post-treatment ]
    For overall survival, Kaplan-Meier plots will be generated for each treatment arm and the curves will be compared using a log rank test. Kaplan-Meier estimates with 95% CI will be summarized every 6 months using Greenwood's formula for the standard error of the Kaplan-Meier estimate. In addition to the Kaplan-Meier estimates, Cox proportional hazards models will be fit to estimate HRs and to assess and adjust for the effects of covariates. Descriptive, subset analysis of OS will be performed for MRD negative patients.
  • Overall survival (OS) [ Time Frame: Time from randomization to the date of death from any cause, assessed up to 2 years post-treatment ]
    For overall survival, Kaplan-Meier plots will be generated for each treatment arm and the curves will be compared using a log rank test. Kaplan-Meier estimates with 95% CI will be summarized every 6 month using Greenwood's formula for the standard error of the Kaplan-Meier estimate. In addition to the Kaplan-Meier estimates, Cox proportional hazards models will be fit to estimate HR's and to assess and adjust for the effects of covariates. Descriptive, subset analysis of OS will be performed for MRD negative patients.
  • Non-relapse mortality (NRM) [ Time Frame: Duration between the date of randomization and the date of patient death due to reasons other than relapse, assessed up to 2 years post-treatment ]
    NRM will be analyzed using competing risks models with deaths due to relapse as a competing risk. Cumulative incidence curves will be generated and treatment effects summarized using the sub-distribution hazard ratio with and without adjustment for covariates
  • Incidence of adverse effects of nivolumab assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 100 days post-treatment ]
    Summary tables for AEs will include only AEs that started or worsened after randomization. The incidence of treatment-related adverse events (new or worsening from baseline after randomization) will be summarized by system organ class and/ or preferred term, severity (based on CTCAE grades), type of adverse event, and relation to study treatment by treatment group. Toxicity rates will be compared between the two treatment arms via chi-squares or Fisher's exact tests.
Not Provided
Not Provided
 
Nivolumab in Eliminating Minimal Residual Disease and Preventing Relapse in Patients With Acute Myeloid Leukemia in Remission After Chemotherapy
Randomized Phase II Study to Assess the Role of Nivolumab as Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Acute Myelogenous Leukemia (AML) Patients After Chemotherapy (Remain Trial)
This randomized 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. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells.

PRIMARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

I. To analyze programmed cell death (PD)-ligand (L)1 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 60 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo standard of care clinical observation for up to 2 years. Upon disease relapse, patients may cross-over to Arm I.

After completion of study treatment, patients are followed up for 2 years.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
Adult Acute Myeloid Leukemia in Remission
  • Other: Clinical Observation
    Undergo standard of care clinical observation
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
  • Experimental: Arm I (nivolumab)
    Patients receive nivolumab IV over 60 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
  • Active Comparator: 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.
    Interventions:
    • Other: Clinical Observation
    • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
Not Provided
June 28, 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • AML patients in first complete remission (CR1) or first complete remission with incomplete blood count recovery (CRi) after induction and consolidation chemotherapy; except young (< 60 years) AML patients in European LeukemiaNet favorable group
  • Within 60 days after bone marrow biopsy confirmed remission after the patients recover from their last course of chemotherapy, the goal will be to consent the eligible patient prior to the remission confirmation bone marrow biopsy at the end of the planned chemotherapy)
  • 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
  • Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status of 0 or 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 6 months
  • Leukocytes >= 2,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • 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)
  • 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
  • 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-programmed cell death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (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; 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; 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 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; 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 should be evaluated for the potential need for additional treatment before coming on study
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Canada,   United States
 
 
NCT02275533
NCI-2014-02167
NCI-2014-02167 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CIRB 15-0185
9706 ( Other Identifier: University of Chicago Comprehensive Cancer Center P2C )
9706 ( Other Identifier: CTEP )
N01CM00071 ( U.S. NIH Grant/Contract )
P30CA014599 ( U.S. NIH Grant/Contract )
UM1CA186644 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Hongtao Liu University of Chicago Comprehensive Cancer Center P2C
National Cancer Institute (NCI)
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP