Clinical Trials /

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

NCT03728335

Description:

This phase I trial studies the side effects of 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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Enasidenib as Maintenance Therapy in Treating Patients With Acute Myeloid Leukemia With IDH2 Mutation After Donor Stem Cell Transplant
  • Official Title: Phase IB Trial of Enasidenib (AG-221) Maintenance Post Allogeneic Hematopoietic Cell Transplantation in Patients With IDH2 Mutation

Clinical Trial IDs

  • ORG STUDY ID: 18117
  • SECONDARY ID: NCI-2018-02371
  • SECONDARY ID: 18117
  • NCT ID: NCT03728335

Conditions

  • Acute Myeloid Leukemia
  • Allogeneic Hematopoietic Stem Cell Transplantation Recipient
  • Blasts Under 5 Percent of Bone Marrow Nucleated Cells
  • IDH2 Gene Mutation
  • Myeloid Leukemia in Remission

Interventions

DrugSynonymsArms
EnasidenibAG-221, CC-90007Treatment (enasidenib)

Purpose

This phase I trial studies the side effects of 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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (enasidenib)ExperimentalPatients receive enasidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
  • Enasidenib

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:Up to 30 days post treatment completion
Safety Issue:
Description:Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:From starting enasidenib to date of death, assessed up to 2 years
Safety Issue:
Description:Will be analyzed using the Kaplan-Meier curves.
Measure:Leukemia free survival (LFS)
Time Frame:From starting enasidenib to date of relapse or death, assessed up to 2 years
Safety Issue:
Description:Will be analyzed using the Kaplan-Meier curves.
Measure:Time to relapse
Time Frame:From starting enasidenib to date of relapse, assessed up to 2 years
Safety Issue:
Description:Time to relapse will be censored at the last disease assessment if patients are known to be alive and leukemia free.
Measure:Non-relapse mortality (NRM)
Time Frame:From starting enasidenib to date of death from other causes than relapse, assessed up to 2 years
Safety Issue:
Description:Will be analyzed using the curves of cumulative incidence.
Measure:Graft versus host disease (GvHD)-free relapse free survival (GRFS)
Time Frame:At 1 year mark of starting enasidenib
Safety Issue:
Description:Will be analyzed using the Kaplan-Meier curves.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:City of Hope Medical Center

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