Nivolumab in Eliminating Minimal Residual Disease and Preventing Relapse in Patients with Acute Myeloid Leukemia in Remission after Chemotherapy

Status: Active

Description

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. 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.

Eligibility Criteria

Inclusion Criteria

  • AML patients in first complete remission (CR) (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; (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 will be 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
  • 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-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 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 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 should be evaluated for the potential need for additional treatment before coming on study

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 205-934-0220
Email: tmyrick@uab.edu

Arizona

Tucson
Banner University Medical Center - Tucson
Status: Active
Contact: Site Public Contact
Email: aselegue@email.arizona.edu
University of Arizona Cancer Center-North Campus
Status: Active
Contact: Site Public Contact
Phone: 800-327-2873

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-826-4673
Email: becomingapatient@coh.org
La Jolla
UC San Diego Moores Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 858-822-5354
Email: cancercto@ucsd.edu
Los Angeles
Los Angeles County-USC Medical Center
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451
Sacramento
University of California Davis Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 916-734-3089

Connecticut

New Haven
Smilow Cancer Center / Yale-New Haven Hospital
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu
Yale University
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: Active
Contact: Site Public Contact
Phone: 202-444-2223

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-679-0775
Email: canceranswers@moffitt.org
Moffitt Cancer Center-International Plaza
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-679-0775
Email: canceranswers@moffitt.org

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
New Lenox
UC Comprehensive Cancer Center at Silver Cross
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
Orland Park
University of Chicago Medicine-Orland Park
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
Peoria
Illinois CancerCare-Peoria
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com

Kansas

Fairway
University of Kansas Clinical Research Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Kansas City
University of Kansas Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 859-257-3379

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-888-8823

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Farmington Hills
Weisberg Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org

Nebraska

Omaha
University of Nebraska Medical Center
Status: Active
Contact: Site Public Contact
Phone: 402-559-6941
Email: unmcrsa@unmc.edu

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-639-6918
Email: cancer.research.nurse@dartmouth.edu

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
Montefiore Medical Center-Einstein Campus
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Contact: Site Public Contact
Phone: 215-955-6084

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Site Public Contact
Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 713-798-1354
Email: burton@bcm.edu
Ben Taub General Hospital
Status: Active
Contact: Site Public Contact
Phone: 713-873-2000

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu

Virginia

Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 804-628-1914
Email: klcampbell@vcu.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922

Ontario

Toronto
University Health Network-Princess Margaret Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 416-946-4501
Email: clinical.trials@uhn.on.ca

Trial Objectives and Outline

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.

EXPLORATORY 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 periodically for 2 years, every 6 months for 1 year, and then yearly thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Chicago Comprehensive Cancer Center EDDOP

Principal Investigator
Hongtao Liu

Trial IDs

Primary ID 9706
Secondary IDs NCI-2014-02167, CIRB 15-0185, CVCIRB 15-0185
Clinicaltrials.gov ID NCT02275533