Clinical Trials /

Study of Enasidenib and Venetoclax in IDH2-Mutated Blood Cancers

NCT04092179

Description:

The purpose of this research study is to see how safe and tolerable, and to find the highest or best dose, of an investigational combination of drugs called enasidenib and venetoclax, in patients with relapsed (the cancer has come back) or refractory (the cancer does not respond or have stopped responding to treatment) acute myeloid leukemia (AML, a type of blood cancer). This study will also see how useful the combination of enasidenib and venetoclax is in the treatment of patients with relapsed or refractory AML.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Enasidenib and Venetoclax in IDH2-Mutated Blood Cancers
  • Official Title: Phase Ib/II Study of IDH2 Inhibitor Enasidenib in Combination With BCL2 Inhibitor Venetoclax in Patients With IDH2-Mutated Myeloid Malignancies (ENAVEN-AML)

Clinical Trial IDs

  • ORG STUDY ID: 19-5939
  • SECONDARY ID: ENAVEN-AML
  • NCT ID: NCT04092179

Conditions

  • Acute Myeloid Leukemia
  • Relapsed Cancer
  • Refractory Cancer
  • IDH2 Gene Mutation

Interventions

DrugSynonymsArms
EnasidenibIDHIFAVenetoclax and Enadisenib
VenetoclaxVENCLEXTAVenetoclax and Enadisenib

Purpose

The purpose of this research study is to see how safe and tolerable, and to find the highest or best dose, of an investigational combination of drugs called enasidenib and venetoclax, in patients with relapsed (the cancer has come back) or refractory (the cancer does not respond or have stopped responding to treatment) acute myeloid leukemia (AML, a type of blood cancer). This study will also see how useful the combination of enasidenib and venetoclax is in the treatment of patients with relapsed or refractory AML.

Detailed Description

      This study will have two parts: Phase 1b and Phase 2. The part that patients may participate
      in will depend on when they join the study.

      In the phase 1b portion of the study, small groups participants will receive increasing doses
      of venetoclax in combination with a flat dose of enadisenib until the highest dose or best
      dose of venetoclax that is safe and tolerable in combination with enadisenib is found.

      In the phase 2 portion of the study, an additional group of participants will receive the
      highest or best dose of venetoclax found in the Phase 1b portion of the study with a flat
      dose of enadisenib to see how useful the combination is in treating relapsed or refractory
      acute myeloid leukemia (AML).
    

Trial Arms

NameTypeDescriptionInterventions
Venetoclax and EnadisenibExperimentalEnasidenib and venetoclax will be taken by mouth (orally), once a day, every day, continuously. Every 28-day period will be called a cycle. Participants will start venetoclax alone on Cycle 1 Day 1 and continue the study drug alone until Day 15. On Day 15, participants will take enasidenib and venetoclax together and will continue to take the combination of study drugs until intolerable side effects or disease worsening.
  • Enasidenib
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance score of ≤2

          -  IDH2 (R140 or IDH R172) mutated AML disease status as determined by local laboratory

          -  Relapsed and/or refractory acute myeloid leukemia (AML). Treatment‐naïve patients who
             are not eligible for standard induction chemotherapy or high‐risk myelodysplastic
             syndromes (MDS) or myeloproliferative neoplasms (MPN) may also be eligible.

          -  Adequate hepatic function

          -  Adequate renal function

          -  Willing and able to provide informed consent

          -  In the absence of rapidly proliferative disease, the interval from prior treatment to
             time of initiation will be at least 7 days for cytotoxic and non‐cytotoxic
             (immunotherapy) agents

        Exclusion Criteria:

          -  Known allergy or hypersensitivity to enasidenib or venetoclax

          -  Previously received either an IDH2 inhibitor or BCL2 inhibitor

          -  With any uncontrolled clinically significant medical conditions

          -  The use of other chemotherapeutic agents or anti‐leukemic agents, radiotherapy or
             other investigational therapy is not permitted during study with exceptions

          -  Receiving concomitant treatment with strong cytochrome P450 2A (CYP3A4) inhibitors
             within 3 days of start of study therapy

          -  Receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin,
             rifampin, rifabutin, St. John's Wort) within 3 days of start of study therapy.

          -  Taking the following sensitive CYP substrate medications that have a narrow
             therapeutic range are excluded from the study unless the subject can be transferred to
             other medications at least 5 half‐lives prior to the start of study treatment:
             paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S‐mephenytoin (CYP2C19),
             thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)

          -  Active graft‐versus‐host‐disease (GVHD) status post stem cell transplant

          -  Severe gastrointestinal or metabolic condition which could interfere with the
             absorption of oral study medications

          -  Concurrent active malignancy under treatment

          -  Administration or consumption of any of the following within 3 days prior to first
             dose of study drug: grapefruit or grapefruits products, Seville oranges (including
             marmalade containing Seville oranges) and start fruit

          -  Heart‐rate corrected QT (QTc) interval ≥480 msec (Fridericia's formula) except for
             underlying right‐bundle branch block (RBBB).

          -  Positive for HIV

          -  Subject has an unacceptable white blood cell count

          -  Positive urine pregnancy test,

          -  Participants who not willing to maintain adequate contraception
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:Dose indicated by the mTPI decision

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:The first day of treatment until death or last contact.
Measure:Event Free Survival
Time Frame:3 years
Safety Issue:
Description:The number of days from the first day of treatment to the date of earliest evidence of relapse or progression, subsequent treatment other than stem cell transplant while in response, or death, or date of last disease assessment.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University Health Network, Toronto

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