Imetelstat Combinations in Relapsed AML

NCT07320235 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY-25-01212PRMC-25-108
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed Acute Myeloid Leukemia

Keywords

IMAGINE Trial; Acute Myeloid Leukemia; AML; Relapsed Acute Myeloid Leukemia; Imetelstat; Imetelstat and Azacitidine

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  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 Outcomes (4)

• Optimal Biological Dose (OBD)

  Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days), for 6 cycles

• Disease-Free Survival (DFS)

  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)

  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)

  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

Study Arms (2)

Part A Safety Run-In phase: Imetelstat in combination with Azacitidine

ACTIVE COMPARATOR

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; Drug: Azacitidine

Part B Combination Therapy: Imetelstat in combination with Azacitidine with or without Venetoclax

ACTIVE COMPARATOR

* 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.

Interventions

Imetelstat DRUG

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

Also known as: GRN163L

Part A Safety Run-In phase: Imetelstat in combination with Azacitidine

Azacitidine DRUG

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.

Part A Safety Run-In phase: Imetelstat in combination with Azacitidine

Venetoclax DRUG

Venetoclax 400mg oral once daily for Days 1 (+/- 1 day) through 14 (+/- 1 day) of each 28-day cycle. Venetoclax reduced dosey should be substituted if concomitant posaconazole, or if other concomitant strong CYP3A4 inhibitor (e.g. voriconazole) or 200mg for moderate CYP3A4 inhibitor (e.g. isavuconazole). For Cycle 1, participants will receive a venetoclax ramp-up dose on day 1, day 2, and days 3-14 of venetoclax,. If the participant is being treated with concomitant posaconazole, or other concomitant strong CYP3A4 inhibitor, or with a concomitant moderate CYP3A4 inhibitor or a pg-p inhibitor, participants will receive a lower ramp-up dose on day 1, day 2, and days 3-14 of venetoclax.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Douglas Tremblay: lead
• Geron Corporation: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

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  BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

imetelstat; GRN163L peptide; Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Douglas Tremblay, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Central Study Contacts

Gabriela Bello

CONTACT

(212) 241-0463; gabriela.bello@mssm.edu

Rashmi Unawane

CONTACT

212-824-2385; rashmi.unawane@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Division of Hematology Oncology

Model Details: 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.

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: January 6, 2026
• Study Start: January 2, 2026
• Primary Completion (Estimated): June 17, 2030
• Study Completion (Estimated): June 15, 2035
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)