Clinical Trial 19136

Cancer Type: Malignant Hematology
Interventions:BMS-936558 (Nivolumab); Nivolumab; Not Applicable

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Kendra Sweet

Overview

Study Title

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)

Summary

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.

Objective

Primary Objectives: To evaluate and compare the progression free survival rate after randomization in the two treatment arms (Nivolumab vs. observation). Secondary Objectives: - To determine and compare the overall survival rates in the two arms. - To determine and compare the incidence of non-relapse mortality in the two arms. - To evaluate the toxicities of Nivolumab as maintenance. Exploratory Objectives: - To analyze PD-LI expression on AML cells from peripheral blood and/or bone marrow samples at diagnosis if available and at the time of study enrollment. - To monitor AML MRD by WT1 PCR at enrollment and at subsequent defined time points in the Nivolumab-treated and control groups. - 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. - 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.

Inclusion Criteria

  • Age 18 years or older
  • Acute Myeloid Leukemia (AML) patients in first complete remission (CR1) or first complete remission with incomplete blood count recovery (CRi) after induction and consolidation chemotherapy; except young (less than 60 years) AML patients in European LeukemiaNet favorable group
  • 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 > 6 months
  • Leukocytes >= 2,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin less than or equal to1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin less than 3.0 mg/dL)
  • Aspartate aminotransferase (AST[SGOT])/alanine aminotransferase (ALT[SGPT]) less than or equal to 2.5 x ULN
  • Amylase and lipase less than or equal 1.5 x ULN without any symptoms of pancreatitis
  • Serum creatinine less than or equal to1.5 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 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; must have a negative serum or urine pregnancy test 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 do not require contraception.
  • Ability to understand and the willingness to sign a written informed consent document

  • Exclusion Criteria

  • Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or have not recovered from adverse events (AEs) due to agents administered > 4 weeks earlier
  • Receiving any other investigational agents
  • Prior treatment with 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 other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • Known central nervous system (CNS) involvement. If disease is cleared before treatment with nivolumab, could be allowed if no permanent CNS damage.
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Uncontrolled intercurrent illness including/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; breastfeeding to be discontinued if mother is treated with nivolumab
  • Known history of testing positive for HIV or known AIDS: might be enrolled if viral load by PCR is undetectable with/without active treatment and absolute lymphocyte count >= 350/ul
  • 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 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; including/not limited to 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; 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 presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
  • May enroll if 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 absence of an external trigger (precipitating event)
  • Patients 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 less than or equal to10 mg daily prednisone equivalents are permitted in absence of active autoimmune disease; patients 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 less than or equal to 10 mg/day prednisone equivalents; brief course of corticosteroids for prophylaxis dye allergy or for treatment of non-autoimmune conditions is permitted.
  • Active/acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis; evaluate potential need for additional treatment before joining study