Acute Myeloid Leukemia Clinical Trial
Enasidenib as Maintenance Therapy in Treating Patients With Acute Myeloid Leukemia With IDH2 Mutation After Donor Stem Cell Transplant
This phase I trial studies the side effects of using enasidenib as maintenance therapy in treating patients with acute myeloid leukemia with IDH2 mutation following donor stem cell transplant. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
I. Evaluate the safety and tolerability of enasidenib mesylate as maintenance therapy in post hematopoietic cell transplantation (HCT) patients.
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 mesylate maintenance therapy.
I. Monitor disease status among subset of patients with minimal residual disease (MRD) positive disease when starting to receive enasidenib mesylate 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.
Patients receive enasidenib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and periodically thereafter up to 2 years.
Documented informed consent of the participant and/or legally authorized representative
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 or Karnofsky performance status (KPS) >= 70
Recipients of allogeneic HCT - all stem cell sources including sibling, unrelated, mismatched related/unrelated, cord and haploidentical transplant patients will be included
Conditioning 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)
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 (rapid plasma reagin [RPR])
If positive, hepatitis C ribonucleic acid (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)
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 weeks
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
Prospective participants, who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
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There are 2 Locations for this study
Duarte California, 91010, United States
Tampa Florida, 33612, United States
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