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Acute Myeloid LeukemiaPhase 1/2NCT04092179

Study of Enasidenib and Venetoclax in IDH2-Mutated Blood Cancers

A Phase 1/2 study testing Enasidenib and Venetoclax in people with Acute Myeloid Leukemia and Relapsed Cancer, run by University Health Network, Toronto at 2 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Enasidenib and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
2 sitesCanada
Study dates
5 Nov 2020to 26 Oct 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 16Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

About this study

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)

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.

Read the 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).

Being tested
Enasidenib, Venetoclax
Medical subject headings
Leukemia, Myeloid, Acute, Recurrence, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnasidenibDrug

    Also called IDHIFA

    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.

  • VenetoclaxDrug

    Also called VENCLEXTA

    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.

Study groups in NCT04092179
Study groupRoleWhat they receive
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.
Receives: Drug: Enasidenib; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR)

    Measured: 3 years

  2. Dose Limiting Toxicity

    Measured: 28 days

  3. Maximum tolerated dose or Recommended Phase 2 Dose

    Dose indicated by the mTPI decision

    Measured: 3 years

  4. Duration of Response

    The time from the date of first response until progression, relapse, death, or last follow-up.

    Measured: 3 years

Secondary outcomes (2)

  1. Overall Survival

    The first day of treatment until death or last contact.

    Measured: 3 years

  2. Event Free Survival

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2019
  2. Study start5 Nov 2020
  3. Primary completion26 Oct 2023
  4. Study completion26 Oct 2023

Why it stopped: Insufficient Funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04092179
Sponsor's protocol ID
19-5939
Other IDs
ENAVEN-AML
Status last verified
Jan 2024
First submitted
13 Sep 2019
Last updated
24 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Richard-Carpentier G, Gupta G, Koraksic C, Cathelin S, Wang L, Bankar A, Davidson M, Gupta V, Maze D, Minden MD, Murphy T, Schimmer AD, Schuh AC, Sibai H, Yee K, DiNardo CD, Brandwein J, McNamara CJ, Chan SM. Enasidenib plus venetoclax in patients with IDH2-mutated relapsed or refractory acute myeloid leukaemia or myelodysplastic syndrome (ENAVEN-AML): a multicentre, single-arm, phase 1b/2 trial. Lancet Haematol. 2025 Nov;12(11):e887-e897. doi: 10.1016/S2352-3026(25)00254-6. Epub 2025 Oct 8.

    PubMed 41075807

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Enasidenib and Venetoclax in people with Acute Myeloid Leukemia and Relapsed Cancer, run by University Health Network, Toronto at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Insufficient Funding). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04092179, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2024.

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