NCT06247787

A Study to Find the Highest Dose of Imetelstat in Combination With Fludarabine and Cytarabine for Patients With AML, MDS or JMML That Has Come Back or Does Not Respond to Therapy

A Phase 1 Study of GRN163L (Imetelstat) in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia That is in Second or Greater Relapse or That is Refractory to Relapse Therapy; Myelodysplastic Syndrome or Juvenile Myelomonocytic Leukemia in First or Greater Relapse or is Refractory to Relapse Therapy

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 1 Year – 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of imetelstat in combination with fludarabine and cytarabine in treating patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML) that has not responded to previous treatment (refractory) or that has come back after a period of improvement (recurrent). Imetelstat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as fludarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving imetelstat in combination with fludarabine and cytarabine may work better in treating patients with refractory or recurrent AML, MDS, and JMML.

Detailed description

PRIMARY OBJECTIVE: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of imetelstat administered in combination with fludarabine and cytarabine to children with second or greater relapse of acute myeloid leukemia or first or greater relapse of myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML). SECONDARY OBJECTIVES: I. To define and describe the toxicities of imetelstat administered on this schedule in combination with fludarabine and cytarabine in patients with refractory and/or relapsed AML, MDS, or JMML. II. To characterize the pharmacokinetics of imetelstat in combination with fludarabine and cytarabine in patients with refractory and/or relapsed AML, MDS, or JMML. III. To describe the antileukemic activity of imetelstat (CR \[complete remission\]/PR \[partial response\]/CRi \[complete remission with incomplete blood count recovery\] and rates of minimal residual disease \[MRD\] negative response after up to two cycles of therapy) in combination with fludarabine and cytarabine within the limits of a phase 1 study. IV. To estimate the overall survival (OS) of children with second or greater relapse of AML or first or greater relapse of MDS or JMML treated with imetelstat administered in combination with fludarabine and cytarabine. EXPLORATORY OBJECTIVES; I. To conduct pharmacodynamics studies of imetelstat in combination with fludarabine and cytarabine in patients with refractory and/or relapsed AML, MDS, or JMML. II. To analyze telomerase activity in peripheral blood mononuclear cells. III. To evaluate baseline and change of cytogenetic abnormalities after treatment with imetelstat in combination with fludarabine and cytarabine. IV. To evaluate baseline mutational status and change of mutational status after treatment with imetelstat in combination with fludarabine and cytarabine. OUTLINE: This is a dose-escalation study of imetelstat. Patients receive imetelstat intravenously (IV) over 2 hours on days 1 and 8, fludarabine IV over 1 hour on days 2-6, and cytarabine IV over 1-3 hours on days 2-6 of each cycle. Patients also receive cytarabine intrathecally (IT) alone or with methotrexate IT, and hydrocortisone IT at the provider's discretion. Patients may also receive leucovorin calcium IV or orally (PO) 24 and 30 hours after each IT triples dose. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO), bone marrow biopsy and/or aspiration, blood sample collection, and lumbar puncture for cerebrospinal fluid (CSF) sample collection during screening and on the trial. After completion of study treatment, patients are followed up for 5 years.

Conditions

• Recurrent Childhood Acute Myeloid Leukemia
• Recurrent Childhood Myelodysplastic Syndrome
• Recurrent Juvenile Myelomonocytic Leukemia
• Refractory Childhood Acute Myeloid Leukemia
• Refractory Childhood Myelodysplastic Syndrome
• Refractory Juvenile Myelomonocytic Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood and CSF sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspiration
DRUG	Cytarabine	Given IV and IT
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Fludarabine	Given IV
DRUG	Hydrocortisone Sodium Succinate	Given IT
BIOLOGICAL	Imetelstat	Given IV
DRUG	Leucovorin Calcium	Given IV or PO
PROCEDURE	Lumbar Puncture	Undergo lumbar puncture
DRUG	Methotrexate	Given IT

Timeline

• Start date: 2025-02-04
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2024-02-08
• Last updated: 2026-02-24

Locations

18 sites across 1 country: United States

Regulatory

• FDA-regulated drug study