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

Recruiting now · Phase 1

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT06247787

Run by

Children's Oncology Group

People needed

36

Starts

2025-02-04

Expected to finish

2028-03-31

Last updated by the study team

2026-04-20

Who can join

Age: 1 and older, up to 18. Sex: any. Healthy volunteers: not accepted.

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
• Extramedullary relapse: Biopsy proven extramedullary disease after documented complete remission
• Refractory disease AML: Following a re-induction cycle after a second relapse, or refractory to two reinduction attempts after either primary induction failure or first relapse with:
• 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 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
• Extramedullary refractory disease:

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

Where it is running

• Children's Hospital of Alabama — Birmingham, Alabama, United States (enrolling)
• Children's Hospital of Orange County — Orange, California, United States (enrolling)
• UCSF Medical Center-Mission Bay — San Francisco, California, United States (enrolling)
• Children's Hospital Colorado — Aurora, Colorado, United States (enrolling)
• Children's National Medical Center — Washington D.C., District of Columbia, United States (enrolling)
• Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States (enrolling)
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States (enrolling)
• Riley Hospital for Children — Indianapolis, Indiana, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• C S Mott Children's Hospital — Ann Arbor, Michigan, United States (enrolling)
• University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States (enrolling)
• Washington University School of Medicine — St Louis, Missouri, United States (enrolling)
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States (enrolling)
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (enrolling)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States (enrolling)
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States (enrolling)
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center — Houston, Texas, United States (enrolling)
• Seattle Children's Hospital — Seattle, Washington, United States (enrolling)

Full record on ClinicalTrials.gov

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