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.
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
Drug | Synonyms | Arms |
---|
Enasidenib | IDHIFA | Venetoclax and Enadisenib |
Venetoclax | VENCLEXTA | Venetoclax 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
Name | Type | Description | Interventions |
---|
Venetoclax and Enadisenib | Experimental | 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. | |
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: | Recruiting |
Lead Sponsor: | University Health Network, Toronto |
Last Updated
May 17, 2021