Nivolumab in AML in Remission at High Risk for Relapse

Phase 2

Completed

Conditions: Adult Acute Myeloid Leukemia in Remission
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Therapy-Related Myeloid Neoplasm
Blasts Under 10 Percent of Bone Marrow Nucleated Cells

Interventions: Other: Laboratory Biomarker Analysis
Biological: Nivolumab

Registration Number: NCT02532231

Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (nivolumab)	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.
Treatment (nivolumab)	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Immunologic Responses to Nivolumab Among Patients With Acute Myeloid Leukemia (AML) in Complete Remission (CR) Status Post Standard Chemotherapy	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.	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
Number of Participants Who Changed From MRD Postive to MRD Negative During Therapy With Nibolumab	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.	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.
Time to Relapse	Up to 7 years 9 months	Time from date of treatment start until the date of first objective documentation of disease-relapse.
Overall Survival	Up to 7 years 9 months	Time from date of treatment start until date of death due to any cause or last Follow-up.