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

NCT06247787 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: PEPN2312NCI-2023-11026UM1CA228823
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 19

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities of imetelstat administered in combination with fludarabine and cytarabine

  Frequency percent (%) of patients with acute myeloid leukemia (AML) in second or greater relapse or refractory to relapse therapy who experience a cycle 1 dose limiting toxicity to imetelstat administered in combination with fludarabine and cytarabine stratified by dose level.

  During cycle 1 of therapy (each cycle is 28 days)

Secondary Outcomes (8)

• Incidence of adverse events of imetelstat administered in combination with fludarabine and cytarabine

  Up to 2 years from study entry

• Area under the drug concentration curve of imetelstat administered in combination with fludarabine and cytarabine

  Up to 24 hours

• Maximum serum concentration of imetelstat administered in combination with fludarabine and cytarabine

  Up to 24 hours

• Clearance of imetelstat administered in combination with fludarabine and cytarabine

  Up to 24 hours

• Half-life of imetelstat administered in combination with fludarabine and cytarabine

  Up to 24 hours

Other Outcomes (4)

• Pharmacodynamics

  Up to 2 years

• Telomerase activity

  Cycle 1 day 1, pre-dose and cycle 1 day 2 at 24 hours (each cycle is 28 days)

• Cytogenetic abnormalities

  At baseline and after cycle 2 (each cycle is 28 days)

Study Arms (1)

Treatment (Imetelstat, fludarabine, cytarabine)

EXPERIMENTAL

Patients receive imetelstat 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 IT alone or with methotrexate IT, and hydrocortisone IT at the provider's discretion. Patients may also receive leucovorin calcium IV or 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 ECHO, bone marrow biopsy and/or aspiration, blood sample collection, and lumbar puncture for CSF sample collection during screening and on the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Procedure: Echocardiography Test; Drug: Fludarabine; Drug: Hydrocortisone Sodium Succinate; Biological: Imetelstat; Drug: Leucovorin Calcium; Procedure: Lumbar Puncture; Drug: Methotrexate

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Imetelstat, fludarabine, cytarabine)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (Imetelstat, fludarabine, cytarabine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (Imetelstat, fludarabine, cytarabine)

Cytarabine DRUG

Given IV and IT

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (Imetelstat, fludarabine, cytarabine)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (Imetelstat, fludarabine, cytarabine)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (Imetelstat, fludarabine, cytarabine)

Hydrocortisone Sodium Succinate DRUG

Given IT

Also known as: (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan, Cortisol Sodium Succinate, Cortop, Efcortelan, Emergent-EZ, Flebocortid, Hidroc Clora, Hycorace, Hydro-Adreson, Hydrocort, Hydrocortisone 21-Sodium Succinate, Hydrocortisone Na Succinate, Kinogen, Nordicort, Nositrol, Sinsurrene, Sodium hydrocortisone succinate, Solu-Cortef, Solu-Glyc

Treatment (Imetelstat, fludarabine, cytarabine)

Imetelstat BIOLOGICAL

Given IV

Also known as: GRN 163L, GRN-163L

Treatment (Imetelstat, fludarabine, cytarabine)

Leucovorin Calcium DRUG

Given IV or PO

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (Imetelstat, fludarabine, cytarabine)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (Imetelstat, fludarabine, cytarabine)

Methotrexate DRUG

Given IT

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (Imetelstat, fludarabine, cytarabine)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be ≥ 1 year and ≤ 18 years of age at the time of study enrollment
• Patients, with or without down syndrome (DS), and with acute myeloid leukemia, therapy-related AML, MDS or JMML and meet one of the following:
• Second or greater relapse or refractory AML, including isolated extramedullary disease (EMD), but excluding isolated central nervous system (CNS) or isolated testicular relapse
• First or greater relapse of MDS
• First or greater relapse of JMML
• For flow cytometry, it's strongly recommended to enroll onto APAL2020SC or to send samples to Hematologics, Inc. Otherwise, assessments must be performed at a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA) certified lab that has expertise in AML.
• For fluorescence in situ hybridization (FISH)/Karyotype, samples must be sent to a Children's Oncology Group (COG)-approved Cytogenetics Lab
• Bone marrow relapse AML: (patients must meet one of the following criteria to be defined as having relapsed disease)
• A single bone marrow sample showing ≥ 5% leukemic blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing, or other molecular method
• A single bone marrow with at least two tests showing ≥ 1% leukemic blasts; examples of tests include:
• Flow cytometry showing ≥ 1% leukemic blasts by multidimensional flow cytometry (MDF)
• Karyotypic abnormality with at least one metaphase similar or identical to diagnosis
• FISH abnormality identical to one present at diagnosis
• Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of leukemogenic lesion identical to diagnosis and ≥ 1%
• In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. A complete blood count documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count ≥ 10,000/uL with ≥ 10% blasts or a WBC count of ≥ 5,000/uL with ≥ 20% blasts) circulating leukemic cells (blasts) can also be used if a bone marrow aspirate or biopsy cannot be performed

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of childbearing potential must use highly effective contraception in addition to a barrier method during treatment and for at least 1 month after the last dose of imetelstat or longer if required by the institutional guidelines for conventional chemotherapy (fludarabine/cytarabine). Male patients who can father a child should use contraception during treatment and for 3 months after the last dose of imetelstat or longer if required by the institutional guidelines for conventional chemotherapy (fludarabine/cytarabine). Imetelstat should not be administered to nursing mothers
• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. Patients may be on physiological doses of steroids (equivalent to ≤ 10 mg prednisone daily for patients ≥ 18 years or ≤ 10mg/m\^2/day \[up to a maximum of 10 mg/day\] for patients \< 18 years). If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy
• Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Specific to MDS patients: Low-grade MDS/refractory cytopenia of childhood (RCC) - MDS with less than 2% blasts in peripheral blood (PB) or less than 5% blasts in the bone marrow (BM) by morphology
• Uncontrolled seizure disorder that is not stabilized with anti-convulsants
• Patient has undergone surgery that requires general anesthesia within 3 weeks before enrollment (line placement/removal/revision or tissue collection is allowed)
• Known hypersensitivity to the study drug or excipients of the preparation
• Patients with acute promyelocytic leukemia (APL) with PML-RARA genetic abnormality according to World Health Organization (WHO) classification or t(15;17) are not eligible
• Patients known to have a congenital bone marrow failure syndrome where increased risk of toxicity may be expected as judged by the Investigator, for example dyskeratosis congenita, are not eligible
• Patients with isolated or refractory CNS or isolated or refractory testicular relapse are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Sponsors & Collaborators

• Children's Oncology Group: lead
• Geron Corporation: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (19)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Juvenile

Interventions

Specimen Handling; Biopsy; Cytarabine; fludarabine; Hydrocortisone; hydrocortisone hemisuccinate; imetelstat; GRN163L peptide; Leucovorin; Spinal Puncture; Methotrexate; merphos

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Aminopterin

Study Officials

• Alexandra M Stevens

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2024
• First Posted: February 8, 2024
• Study Start: February 4, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (19)