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AzTrials

Recurrent Childhood Acute Myeloid LeukemiaPhase 1NCT06247787

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 testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Childhood Acute Myeloid Leukemia and Recurrent Childhood Myelodysplastic Syndrome, run by Children's Oncology Group at 19 sites in United States.

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Trial 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… Read more about this study

Who is it for?
Ages 1 year to 18 years
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
19 sitesUnited States
Study dates
4 Feb 2025to 31 Mar 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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:
  • Biopsy proven persistent extramedullary disease
  • 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/ µL (i.e., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count of ≥ 5,000/μL with ≥ 20% blasts) circulating leukemic cells (blasts) can also be used if a bone marrow aspirate or biopsy cannot be performed
  • Central nervous system disease: Patients with relapsed or refractory disease with central nervous system (CNS) 1 and CNS 2 status are eligible
  • MDS: Bone marrow relapse: (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, FISH, 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 MDS associated 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
  • JMML: Diagnosis: Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease. The diagnosis is made based on the following criteria
  • JMML category 1 (all of the following):
  • Splenomegaly
  • > 1000 (1 x 10^9 /uL) circulating monocytes
  • < 20% Blasts in the bone marrow or peripheral blood
  • Absence of the t(9;22) or BCR/ABL fusion gene
  • The diagnostic criteria must include all features in category 1 and either (i) one of the features in category 2 or (ii) two features from category 3 to make the diagnosis
  • JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
  • Somatic mutation in RAS or PTPN11
  • Clinical diagnosis of NF1 or NF1 gene mutation
  • Homozygous mutation in CBL
  • Monosomy 7
  • JMML category 3 (at least two of the following if no category 2 criteria are met):
  • Circulating myeloid precursors
  • White blood cell count, > 10,000 (10 x 10^9 / uL)
  • Increased hemoglobin F for age
  • Clonal cytogenetic abnormality
  • Granulocyte-macrophage-colony-stimulating factor (GM-CSF) hypersensitivity
  • Patients with relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) hypomethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality. Frontline therapy is defined as one cycle of intravenous chemotherapy that includes of any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine. Frontline therapy will also include any conditioning regimen as part of a stem cell transplant. Patients who transform to AML at any point with more than 20% blasts are eligible for this trial per the AML specific criteria
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky (≥ 50) for patients > 16 years of age and Lansky for patients ≤ 16 years of age (≥ 50)
  • Patients must have fully recovered (grade < 2) from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required time frame, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
  • NOTE: IT therapy does not require a washout period
  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See DVL homepage on the COG Members site for commercial and investigational agent classifications (https://cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf). For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
  • ≥ 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy
  • Note: Cytoreduction with hydroxyurea must be discontinued ≥ 24 hours prior to the start of protocol therapy
  • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil [ANC] counts):
  • ≥ 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
  • Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
  • Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon, or cytokines (other than hematopoetic growth factors)
  • Stem cell Infusions (with or without total body irradiation [TBI]):
  • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: ≥ 84 days after infusion and no evidence of graft-versus-host disease (GVHD)
  • Patients must be off calcineurin inhibitors for at least 28 days prior to the date of enrollment. 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)
  • Autologous stem cell infusion including boost infusion: ≥ 30 days
  • Cellular Therapy: ≥ 30 days after the completion of any type of cellular therapy (eg, modified T cells, natural killer [NK] cells, dendritic cells, etc.)
  • External Beam Radiation (XRT)/external beam irradiation including protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow (BM) radiation
  • Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I MIBG): ≥ 42 days after systemically administered radiopharmaceutical therapy
  • Patients must not have received prior exposure to imetelstat
  • For patients with leukemia:
  • Platelet count ≥ 25,000/uL (may receive platelet transfusions). These patients must not be known to be refractory to red cell or platelet transfusion
  • Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
  • Adequate renal function defined as:
  • Estimated glomerular filtration rate (GFR) (eGFR) ≥ 70 mL/min/1.73 m^2 OR
  • a 24 hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 OR
  • a GFR ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
  • Adequate liver function defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 3 x ULN, unless attributed to leukemia involvement
  • AST ≤ 3 x ULN, unless attributed to leukemia involvement
  • Albumin ≥ 2 g/dL
  • Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by gated radionuclide study

Who cannot join

  • 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
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  • 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

Trial locations and contacts

19 sites in 1 country. Contact the study team or a site near you to ask about taking part.

19 sites in 1 country

United States19 sites, 18 recruiting

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

    Site Public Contact, 800-865-1125

    Rajen Mody

    Recruiting

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

    Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org

    Jason R. Fangusaro

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org

    Margaret E. Macy

    Recruiting

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

    Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu

    Girish Dhall

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Site Public Contact, 877-442-3324

    Jonathan Paolino

    Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

    Site Public Contact, 773-880-4562

    Sara Zarnegar-Lumley

    Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

    Site Public Contact, 513-636-2799, cancer@cchmc.org

    Joseph G. Pressey

    Recruiting

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 713-798-1354, burton@bcm.edu

    Alexandra M. Stevens

    Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

    Site Public Contact, 800-248-1199

    Brian D. Weiss

    Recruiting

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

    Site Public Contact, 888-226-4343, referralinfo@stjude.org

    Matthew Rees

    Recruiting

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

    Site Public Contact, 612-624-2620

    Robin L. Williams

    Recruiting

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

    New York, New York, 10032

    Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Nobuko Hijiya

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, 92868

    Site Public Contact, 714-509-8646, oncresearch@choc.org

    Elyssa M. Rubin

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu

    Sarah K. Tasian

    Recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

    Site Public Contact, 412-692-8570, jean.tersak@chp.edu

    Andrew Bukowinski

    Recruiting

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

    Site Public Contact, 877-827-3222, cancertrials@ucsf.edu

    Kieuhoa T. Vo

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Suspended

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Shalini Shenoy

    Recruiting

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

    Site Public Contact, 202-476-2800, OncCRC_OnCall@childrensnational.org

    AeRang Kim

    Recruiting

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Cytarabine, Echocardiography Test
Medical subject headings
Leukemia, Myelomonocytic, Juvenile

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and CSF sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • CytarabineDrug

    Also called .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

    Given IV and IT

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Hydrocortisone Sodium SuccinateDrug

    Also called (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan

    Given IT

  • ImetelstatBiological

    Also called GRN 163L, GRN-163L

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV or PO

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IT

Study groups in NCT06247787
Study groupRoleWhat they receive
Treatment (Imetelstat, fludarabine, cytarabine)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)

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

    Frequency (%) of patients with acute myeloid leukemia in second or greater relapse or refractory to relapse therapy who experience adverse events at least possibly attributable to imetelstat administered in combination with fludarabine and cytarabine stratified by dose level graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 2 years from study entry

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

    Median (minimum [min], maximum [max]) of the area under the drug concentration curve of imetelstat administered in combination with fludarabine and cytarabine assessed during cycle 1 at 0, 0.5, 1, 4-5, 6-8 and 24-hours post administration.

    Measured: Up to 24 hours

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

    Median (min, max) of the maximum serum concentration of imetelstat administered in combination with fludarabine and cytarabine assessed during cycle 1 at 0, 0.5, 1, 4-5, 6-8 and 24-hours post administration.

    Measured: Up to 24 hours

  4. Clearance of imetelstat administered in combination with fludarabine and cytarabine

    Median (min, max) of the clearance of imetelstat administered in combination with fludarabine and cytarabine assessed during cycle 1 at 0, 0.5, 1, 4-5, 6-8 and 24-hours post administration.

    Measured: Up to 24 hours

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

    Median (min, max) of the half-life of imetelstat administered in combination with fludarabine and cytarabine assessed during cycle 1 at 0, 0.5, 1, 4-5, 6-8 and 24-hours post administration.

    Measured: Up to 24 hours

  6. PK parameters: Volume of distribution

    Median (min, max) volume of distribution of imetelstat administered in combination with fludarabine and cytarabine assessed during cycle 1 at 0, 0.5, 1, 4-5, 6-8, and 24 hours post administration.

    Measured: Up to 24 hours

  7. Antileukemic activity of imetelstat administered in combination with fludarabine and cytarabine

    Frequency (%) of patients with best overall response of complete remission, partial response, or complete remission with incomplete blood count recovery after up to two cycles of therapy with imetelstat administered in combination with fludarabine and cytarabine.

    Measured: Up to 56 days

  8. Overall survival (OS) of imetelstat administered in combination with fludarabine and cytarabine

    Kaplan-Meier survival curves will estimate the median (95% CI) overall time-to-death due to any cause and stratified by dose level.

    Measured: Up to 5 years from study entry

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2024
  2. Study start4 Feb 2025
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06247787
Sponsor's protocol ID
PEPN2312
Other IDs
NCI-2023-11026, PEPN2312, PEPN2312, UM1CA228823
Status last verified
Apr 2026
First submitted
18 Jan 2024
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Childhood Acute Myeloid Leukemia and Recurrent Childhood Myelodysplastic Syndrome, run by Children's Oncology Group at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 88 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities of imetelstat administered in combination with fludarabine and cytarabine (time frame: During cycle 1 of therapy (each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06247787.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.

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