Health TrialsbyHealthPanel

Imetelstat Combinations in Relapsed AML

ConditionRelapsed Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorDouglas Tremblay

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Participants must have a life expectancy of at least 12 weeks per investigator.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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

  • 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.

  • 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.

Treatment groups

36 Participants
are divided into 2 treatment groups
Group A: Part A Safety Run-In phase: Imetelstat in combination with AzacitidineActive comparator 2 interventions
Group B: Part B Combination Therapy: Imetelstat in combination with Azacitidine with or without VenetoclaxActive comparator 0 interventions

Trial outcomes

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.

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

Secondary outcomes

1

Optimal Biological Dose (OBD)

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.

Time frame
Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days), for 6 cycles
2

Disease-Free Survival (DFS)

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.

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
3

Duration of Response (DOR)

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.

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
4

Overall Survival (OS)

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.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Douglas Tremblay

Lead sponsor

Icahn School of Medicine at Mount Sinai

Sponsor institution

Geron Corporation

Collaborator

Source ClinicalTrials.gov
Apply now