Nivolumab in AML in Remission at High Risk for Relapse

PD-1 Inhibition With Nivolumab for the Treatment of Patients With Acute Myeloid Leukemia in Remission at High Risk for Relapse

This phase II trial studies how well nivolumab works in treating patients with acute myeloid leukemia that has decreased or disappeared but may still be in the body (remission), and is at high risk for returning (relapse). 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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Therapy-Related Myeloid Neoplasm
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the anti-leukemic effects of nivolumab in patients with acute myeloid leukemia (AML) who have achieved a 1st complete remission (CR) after induction chemotherapy and consolidation chemotherapy and have high risk for relapse, or have achieved a 2nd CR.

SECONDARY OBJECTIVES:

I. To evaluate the immunologic responses to nivolumab among patients with AML in CR status post standard chemotherapy.

II. To determine whether response to nivolumab correlates with immunologic responses.

III. To evaluate assessment of minimal residual disease (MRD) by flow cytometry as a predictor of response to immune therapy in treatment of AML and changes during the course of therapy with nivolumab.

IV. To evaluate time to relapse and overall survival. V. To evaluate the toxicity profile of nivolumab among patients with AML in CR.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle.

After completion of study treatment, patients are followed up for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with AML in remission (defined as CR, CR with incomplete platelet recovery -CRp-, CR with incomplete hematologic recovery -CRi-, or partial remission defined as a bone marrow with < 10% blasts after therapy with or without hematologic recovery)
• High risk for relapse defined as: 1st CR with high risk features for relapse (including history of prior malignancy treated with chemotherapy or radiotherapy, or history of myelodysplastic syndrome, myeloproliferative disorder, chronic myelomonocytic leukemia, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN] or other hematologic malignancy thought to have evolved to AML [i.e., secondary AML, (sAML)]; high risk cytogenetics at diagnosis; fms-related tyrosine kinase 3 [FLT3] mutated at diagnosis; or presence or minimal residual disease assessed by polymerase chain reaction [PCR], cytogenetics, and/or flow cytometry at time of enrollment) 2nd CR regardless of disease characteristics at the time of diagnosis
• Have received induction chemotherapy and at least one cycle of consolidation chemotherapy; patients should have achieved a CR within 12 months of enrollment onto protocol
• No further chemotherapy or stem cell transplant (SCT) planned at the time of enrollment
• Creatinine =< 1.5 x upper limit of normal (ULN)
• Serum bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (b-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 23 weeks after the last dose of the study drug; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
• Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drug
• Patients or their legally authorized representative must provide written informed consent

Exclusion Criteria:

• History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
• Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs
• Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association [NYHA] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study
• Patients unwilling or unable to comply with the protocol
• Patients who are on steroids (> 10 mg/day or equivalent) or immune suppression medications
• Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])
• Patients with a history of inflammatory bowel disease such as Crohn's disease and ulcerative colitis
• Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months), or with known human immunodeficiency virus (HIV) infection
• Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents
• Females who are pregnant or lactating
• Patients with history of previous immunomodulatory therapy (not including lenalidomide or thalidomide)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (nivolumab); Patients receive nivolumab IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle.

Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival Rate	Time from date of treatment start until the date of first objective documentation of disease-relapse.	Up to 7 years 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Immunologic Responses to Nivolumab Among Patients With Acute Myeloid Leukemia (AML) in Complete Remission (CR) Status Post Standard Chemotherapy	Participants with Immunologic responses to nivolumab among patients with acute myeloid leukemia (AML) in complete remission (CR) status post standard chemotherapy. CR is Neutrophil count >/= 1.0 x 10^9/L, with a platelet count of >/+ x 10 ^ 9/L	Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.
Number of Participants Who Changed From MRD Postive to MRD Negative During Therapy With Nibolumab	Assessed by flow cytometry as a predictor of response to immune therapy in treatment of AML. The number of participants who were MRD Positive at the start of therapy with nivolumab and changed to MRD Negative during treatment.	Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.
Time to Relapse	Time from date of treatment start until the date of first objective documentation of disease-relapse.	Up to 7 years 9 months
Overall Survival	Time from date of treatment start until date of death due to any cause or last Follow-up.	Up to 7 years 9 months

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Tapan M Kadia, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2015
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: August 21, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimated): August 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: 2015-0213 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2015-01522 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No