Enasidenib as Maintenance Therapy in Treating Patients With Acute Myeloid Leukemia With IDH2 Mutation After Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. Evaluate the safety and tolerability of enasidenib as maintenance therapy in post
hematopoietic cell transplantation (HCT) patients.

SECONDARY OBJECTIVES:

I. Assess overall and leukemia free survival in patients post allogeneic HCT. II. Estimate
relapse incidence, non-relapse mortality, graft versus host disease (GVHD) and relapse free
survival (GRFS) in patients receiving enasidenib maintenance therapy.

EXPLORATORY OBJECTIVES:

I. Monitor disease status among subset of patients with MRD positive disease when start to
receive enasidenib by multiparameter flow cytometry post allogeneic HCT on patients bone
marrow (BM) on days +100 and +365.

II. Investigate clearance of IDH2 mutation post HCT by next generation sequencing-polymerase
chain reaction (NGS-PCR) testing on the bone marrow specimens on days +100 and +365 and in
peripheral blood every 3 months till 2 year follow up.

III. Investigate mIDH2 variant allele fraction (VAF) by droplet digital PCR (ddPCR) BEAMing
technology on bone marrow specimens on days +100 and +365.

OUTLINE:

Patients receive enasidenib orally (PO) once daily (QD) on days 1-28. Treatment repeats every
28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and periodically
thereafter.

Inclusion Criteria:

- Documented informed consent of the participant and/or legally authorized
representative

- Assent, when appropriate, will be obtained per institutional guidelines

- Agreement to allow the use of archival tissue from diagnostic tumor biopsies

- If unavailable, exceptions may be granted with Study principal investigator (PI)
approval.

- Eastern Cooperative Oncology Group (ECOG) =< 2

- Ability to read and understand English or Spanish for questionnaires

- Recipients of allogeneic HCT - all stem cell sources including sibling, unrelated,
mismatched related/unrelated, cord and haploidentical transplant patients will be
included

- CONDITIONAL REGIMEN: Investigator's choice based on center guidelines

- GvHD PROPHYLAXIS: Sirolimus + Tacrolimus or Tacrolimus + Methotrexate or investigator
choice

- Patients must have acute myeloid leukemia (AML) with IDH2 mutation at diagnosis. Day
30 marrow post HCT should show evidence of morphologic remission with < 5% bone marrow
blasts. Patients with MRD either by flow cytometry or IDH2 mutation testing will be
allowed

- Patients with previous therapy with IDH2 inhibitors will be included

- Absolute neutrophil count (ANC) > 1000 (performed within 28 days prior to Day 1 of
protocol therapy unless otherwise stated)

- Hemoglobin >= 9.5 gm% (performed within 28 days prior to Day 1 of protocol therapy
unless otherwise stated)

- Platelets > 50,000/mm^3 (performed within 28 days prior to Day 1 of protocol therapy
unless otherwise stated)

- Platelets >= 20,000/mm^3 (performed within 28 days prior to Day 1 of protocol therapy
unless otherwise stated)

- NOTE: Patients with lower counts can enroll if infection cytomegalovirus
(CMV)/human herpesvirus 6 (HHV6) etc. is being treated actively

- Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
(performed within 28 days prior to Day 1 of protocol therapy unless otherwise stated)

- ECOG =< 2 (performed within 28 days prior to day 1 of protocol therapy unless
otherwise stated)

- Total bilirubin < 2.0 mg/dl-exception permitted in patients with Gilbert's Syndrome
(performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

- Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2 x ULN), Patients with abnormal liver function tests (LFTs) in the context of
active GVHD will not be included (performed within 28 days prior to day 1 of protocol
therapy unless otherwise stated)

- Creatinine clearance of >= 40/min/1.73 m^2 for participants with creatinine levels
above institutional normal per 24 hour urine test or the Cockcroft-Gault formula
(performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

- Corrected QT (QTc) =< 480 ms

- Note: To be performed within 28 days prior to day 1 of protocol therapy

- Seronegative for human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab) combo,
hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative),
and syphilis (RPR)

- If positive, Hepatitis C RNA quantitation must be performed

- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required

- Agreement by females and males of childbearing potential to use an effective method of
birth control or abstain from heterosexual activity for the course of the study
through at least 3 months after the last dose of protocol therapy.

- Childbearing potential defined as not being surgically sterilized (men and women)
or have not been free from menses for > 1 year (women only).

Exclusion Criteria:

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to study agent

- Active diarrhea considered clinically significant and may impair oral drug
administration

- Clinically significant uncontrolled illness

- Active infection requiring antibiotics

- Active infection. Patients with treated viral, bacterial or fungal infections
that are controlled on therapy will be allowed to participate

- Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection

- Diagnosis of Gilbert's disease

- Other active malignancy. Participants with history of prior malignancy treated with
curative intent who achieved complete response (CR) more than 2 years before study
entry are eligible. This exclusion rule does not apply to non-melanoma skin tumors and
in-situ cervical cancer

- FEMALES ONLY: Pregnant or breastfeeding

- Active Grade II-IV acute GVHD and/or requiring systemic steroids with prednisone dose
equivalent of >= 0.25 mg/kg at end of 4 week

- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures