Imetelstat Combinations in Relapsed AML (IMAGINE)

April 17, 2026 updated by: Douglas Tremblay

IMetelstat and Azacitidine With or Without Venetoclax GIveN in rElapsed Acute Myeloid Leukemia (IMAGINE Trial)

IMAGINE is a two-part trial to evaluate the safety and preliminary efficacy of imetelstat in combination with azacitidine with or without venetoclax in patients with relapsed or refractory AML. The trial will consist of a safety run-in phase (Part A) employing a 3+3 design to monitor dose-limiting toxicities of imetelstat when administered in combination with a fixed dose of azacitidine. Part B will consist of a phase 1b trial employing a BOIN12 design to determine the optimal biological dose of imetelstat, starting at a lower dose level, in combination with azacitidine and venetoclax. Total of up to 36 participants will be accrued over 54 months at Mount Sinai Hospital. Estimated duration of trial is 114 months including recruitment, screening, treatment, and follow-up.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • ICAHN School of Medicine at Mount Sinai
        • Principal Investigator:
          • Douglas Tremblay
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria In order to be eligible for participation in this trial,

  • Participants must be ≥18 years of age at time of signing the Informed Consent Form (ICF).
  • Participants must voluntarily sign an ICF.

  • Participants must have WHO-confirmed non-APL AML who have not responded to or relapsed after at least one prior therapy and for whom no standard therapy that may provide clinical benefit is available.

    o Participants with isolated extramedullary disease (EMD), including leukemia cutis, are included but not those with active known CNS disease.

  • Participants must have a life expectancy of at least 12 weeks per investigator.
  • ECOG performance status ≤ 3.
  • Women of child bearing potential (WOCBP), defined as a sexually mature woman not surgically sterilized or post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if >55 years, must have a negative serum pregnancy test at screening and cycle 1 day 1 and must agree to use highly effective methods of birth control starting with the first dose of study therapy through 6 months after the last dose of study therapy. Highly effective methods of contraception include double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence

  • Male participants should agree to use a highly effective method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy. 8. Must have adequate organ function as demonstrated by the following:

    • Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless considered due to leukemic organ involvement or Gilbert's syndrome.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
    • Creatinine clearance (CrCl) ≥ 30 mL/min (measured or estimated by Cockcroft-Gault formula).
  • Ability to adhere to the study visit schedule and all protocol requirements.
  • Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria The participant must be excluded from participating in the trial if the participant:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks or within 5 half-lives of the prior investigational agent, whichever is shorter, of the first dose of treatment.
  • Known clinically active central nervous system (CNS) leukemia. a. Prior CNS leukemia will be allowed if the most recent cerebral spinal fluid sample is negative prior to study initiation and there is no clinical suspicion for active CNS disease.
  • Has a white blood cell count > 25 x 109/L (hydroxyurea and/or continuous cytarabine ≤1 g/m2 is permitted to meet this criterion).
  • Active Graft Versus Host Disease (GVHD), or any GVHD requiring treatment with immunosuppression, with the exception of topical steroids and systemic steroids at a dose equivalent to prednisone 10mg or less. Any GVHD treatment (including calcineurin inhibitors) must be discontinued at least 28 days prior to Day 1 of study treatment.
  • Participants with a history of other cancers must not be receiving active treatment (with radiation or chemotherapy) and must be free of disease for 2 years prior to the Screening Visit with the exception of localized prostate cancer treated with hormone therapy, breast cancer treated with hormone therapy, localized basal cell carcinoma, non-melanoma skin cancer, cervical carcinoma in situ, concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the participant is not receiving any systemic therapy or radiation
  • Myocardial infarction or unstable angina within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
  • Presence of active serious infection. a. If a participant is identified to have COVID-19 during the screening period, participants may be considered eligible if in the opinion of the investigator there are no COVID-19 sequelae that may place the participant at a higher risk of receiving investigational treatment
  • Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the participant from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Known history of uncontrolled human immunodeficiency virus (HIV)
  • Active known systemic hepatitis A, B, or C infection requiring therapy or known cirrhosis.
  • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or pharmaceutical sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific participant.
  • Organ transplant recipients other than bone marrow transplant.
  • Women who are pregnant or lactating.
  • Participants with known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of venetoclax, including difficulty swallowing, are not eligible (Part B only).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Part A Safety Run-In phase: Imetelstat in combination with Azacitidine

Part A combination therapy:

  • Imetelstat will be administered on Day 1 of each 28-day cycle
  • Azacitidine once daily for Days 1 (+/- 1 day) through 7 (+/- 1 day) of each 28-day cycle.
Drug: Imetelstat
Three 3 dose levels administered on Day 1 of each 28-day cycle for Safety Run-in Phase and optimal dose to be administered on Day 1 of each 28-day cycle
Other Names:
  • GRN163L
Drug: Azacitidine
75mg/m2 IV or subcutaneous (SQ) once daily for Days 1 (+/- 1 day) through 7 (+/- 1 day) of each 28-day cycle. Azacitidine can be administered locally as long as documentation of administration is provided to the study team.
Active Comparator: Part B Combination Therapy: Imetelstat in combination with Azacitidine with or without Venetoclax
  • Imetelstat will be administered on Day 1 of each 28-day cycle
  • Azacitidine once daily for Days 1 (+/- 1 day) through 7 (+/- 1 day) of each 28-day cycle.
  • Venetoclax once daily for Days 1 (+/- 1 day) through 14 (+/- 1 day) of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicity (DLT)
Time Frame: Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days), for 6 cycles
The DLT-evaluable population includes participants in the Part A portion of the trial who received at least one dose of imetelstat and azacitidine and either experienced a Dose-Limiting Toxicity (DLT) during the first-cycle DLT assessment period or completed their first-cycle DLT assessment.
Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days), for 6 cycles

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Optimal Biological Dose (OBD)
Time Frame: Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days), for 6 cycles

The OBD-evaluable population includes participants in the Part B portion of the trial who received at least one dose of imetelstat, azacitidine, and venetoclax and either experienced a Dose-Limiting Toxicity (DLT) during the first-cycle DLT assessment period or completed their first-cycle DLT assessment.

Optimal Biological Dose (OBD) is defined as the lowest safe dose providing the highest rate of efficacy.
Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days), for 6 cycles
Disease-Free Survival (DFS)
Time Frame: Cycle 1 Day 1 (each cycle is 28 days) until the first documented evidence of relapsed disease or death from any cause, or up to 6 months. whichever occurs first
Disease-Free Survival (DFS) is defined as the time from the first occurrence of CR, CRh, or CRi, based on ELN 2022 response criteria (which, in this study, can only be assessed at cycles 2, 4, or 6), until the first documented evidence of relapsed disease or death from any cause, whichever occurs first.Participants who do not achieve CR, CRh, or CRi at one of their cycle 2, 4, or 6 assessments will be excluded from this analysis.
Cycle 1 Day 1 (each cycle is 28 days) until the first documented evidence of relapsed disease or death from any cause, or up to 6 months. whichever occurs first
Duration of Response (DOR)
Time Frame: Cycle 1 Day 1 (each cycle is 28 days) until the first documented evidence of relapsed disease or death from any cause, or up to 6 months whichever occurs first
Duration of Response (DOR) is defined as the time from the first occurrence of CR, CRh, CRi, MLFS, or PR based on ELN 2022 response criteria (which, in this study, can only be assessed at D22 of cycles 2, 4, or 6), until the first documented evidence of relapsed disease or death from any cause, whichever occurs first. Participants who do not achieve CR, CRh, Cri, MLFS, or PR at one of their cycle 2, 4, or 6 assessments will be excluded from this analysis.
Cycle 1 Day 1 (each cycle is 28 days) until the first documented evidence of relapsed disease or death from any cause, or up to 6 months whichever occurs first
Overall Survival (OS)
Time Frame: Cycle 1 Day 1 (each cycle is 28 days) to the date of death, regardless of the actual cause of death, or or up to 5 years, whichever comes first
Overall Survival (OS) is defined as the time from C1D1 to the date of death, regardless of the actual cause of the participant's death. For participants who are still alive at the time of data analysis or who are lost to follow-up, OS time will be censored at the last recorded date that the participant is known to be alive as of the data cut-off date for the analysis.
Cycle 1 Day 1 (each cycle is 28 days) to the date of death, regardless of the actual cause of death, or or up to 5 years, whichever comes first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Douglas Tremblay

Collaborators

Geron Corporation

Investigators

  • Study Chair: John Mascarenhas, MD, ICAHN School of Medicine at Mount Sinai
  • Principal Investigator: Douglas Tremblay, MD, ICAHN School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2026

Primary Completion (Estimated)

June 17, 2030

Study Completion (Estimated)

June 15, 2035

Study Registration Dates

First Submitted

December 9, 2025

First Submitted That Met QC Criteria

January 5, 2026

First Posted (Actual)

January 6, 2026

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 17, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY-25-01212
  • PRMC-25-108 (Other Identifier: TCI PRMC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD sharing plan is Undecided.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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