- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04092179
Study of Enasidenib and Venetoclax in IDH2-Mutated Blood Cancers
Phase Ib/II Study of IDH2 Inhibitor Enasidenib in Combination With BCL2 Inhibitor Venetoclax in Patients With IDH2-Mutated Myeloid Malignancies (ENAVEN-AML)
Study Overview
Status
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Steven Chan, M.D.
- Phone Number: 416-946-2253
- Email: steven.chan@uhn.ca
Study Contact Backup
- Name: Sara Newton
- Email: sara.newton@uhn.ca
Study Locations
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-
Alberta
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Edmonton, Alberta, Canada, T6G 2B7
- University of Alberta Hospital
-
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Ontario
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Toronto, Ontario, Canada, M5G 1Z5
- Princess Margaret Cancer Centre
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Venetoclax and Enadisenib
Enasidenib 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 is a drug that blocks a protein called isocitrate dehydrogenase (IDH) 2 from working.
The family of IDH proteins have been indicated in the development of leukemia.
By blocking IDH2, enasidenib may help stop cancer cells from growing.
It is believed that the drug may be more useful in patients with a change (mutation) in their IDH 2 protein.
The IDH2 gene (substances in the body that contain instructions for the proper development and function of cells) makes IDH2 proteins.
As such, only patients with IDH 2 mutated gene are eligible for this study.
Enasidenib is currently approved for the treatment of IDH2 mutated AML.
Other Names:
Venetoclax is a drug that blocks a protein called B-cell lymphoma (BCL2) protein from working.
BCL2 is a protein that helps control whether a cell lives or dies and is thought to help cancer cells to live.
Blocking BCL2 is believed to help kill cancer cells.
Venetoclax is currently approved for the treatment of type of blood cancer called chronic lymphocytic leukemia (CLL) who have received prior treatment.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR)
Time Frame: 3 years
|
3 years
|
|
Dose Limiting Toxicity
Time Frame: 28 days
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28 days
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Maximum tolerated dose or Recommended Phase 2 Dose
Time Frame: 3 years
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Dose indicated by the mTPI decision
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3 years
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Duration of Response
Time Frame: 3 years
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The time from the date of first response until progression, relapse, death, or last follow-up.
|
3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 3 years
|
The first day of treatment until death or last contact.
|
3 years
|
Event Free Survival
Time Frame: 3 years
|
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.
|
3 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Steven Chan, M.D., Princess Margaret Cancer Centre
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19-5939
- ENAVEN-AML (Other Identifier: Princess Margaret Cancer Centre)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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