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.
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)
