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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Acute Myeloid Leukemia; Recurrent Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory Myelodysplastic Syndrome; Recurrent Juvenile Myelomonocytic Leukemia
• Intervention / Treatment: Procedure: Lumbar Puncture; Procedure: Echocardiography; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Fludarabine; Drug: Cytarabine; Drug: Hydrocortisone Sodium Succinate; Biological: Imetelstat; Drug: Leucovorin Calcium; Drug: Methotrexate

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 preliminarily describe the antileukemic activity of imetelstat (complete remission [CR]/CR with incomplete platelet counts [CRp]/CR with incomplete hematologic recovery [CRi] 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.

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 imeletstat.

Patients receive imeletstat 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) or methotrexate IT, and hydrocortisone IT at the provider's discretion. Patients then 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 aspirate, blood sample collection, and lumbar puncture for cerebrospinal fluid (CSF) sample collection during screening and on the trial.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 de novo 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

• AML: 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, fluorescence in situ hybridization (FISH) testing done at a Childrens Oncology Group (COG)-approved laboratory, 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 (performed at a COG-approved laboratory) with at least one metaphase similar or identical to diagnosis
    • Fluorescence in situ hybridization (FISH) abnormality (performed at a COG-approved laboratory) 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 first relapse with the presence of ≥ 1% leukemic blasts by flow cytometry performed at a COG-approved laboratory, OR there is 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/ 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
• 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 testing done at a COG-approved laboratory, 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 (performed at a COG-approved laboratory) with at least one metaphase similar or identical to diagnosis
    • FISH abnormality (performed at a COG-approved laboratory) 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 (1x10^9 /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 andeither (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 (10x10^9 / 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) demethylating 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

• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See DVLhomepage 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 Ccoordinator 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/m2/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, 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)

• A creatinine based on age/gender or - a 24 hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 or a glomerular filtration rate (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)

  • Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility

• Patients with leukemias:

  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 225 U/L, unless attributed to leukemia involvement. For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Albumin ≥ 2 g/dL
• Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by gated radionuclide study

Exclusion Criteria:

• 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. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (Imetelstat, fludarabine, cytarabine); Patients receive imeletstat 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 or methotrexate IT, and hydrocortisone IT at the provider's discretion. Patients then 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 aspirate, blood sample collection, and lumbar puncture for CSF sample collection during screening and on the trial.

Procedure: Lumbar Puncture; Undergo lumbar puncture; Other Names: LP; Spinal Tap; Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy and aspiration; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow; Procedure: Biospecimen Collection; Undergo blood and CSF sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Bone Marrow Aspiration; Undergo bone marrow biopsy and aspiration; Drug: Fludarabine; Receive IV; Other Names: Fluradosa; Drug: Cytarabine; Receive IV and IT; Other Names: .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; Drug: Hydrocortisone Sodium Succinate; Receive IT; Other Names: (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; Biological: Imetelstat; Receive IV; Other Names: GRN 163L; Drug: Leucovorin Calcium; Receive IV or PO; Other Names: Wellcovorin; 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 Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Folinic acid; Drug: Methotrexate; Receive IT; Other Names: Abitrexate; Folex; Mexate; MTX; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate-AQ; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose and recommended phase 2 dose of imetelstat administered in combination with fludarabine and cytarabine	During cycle 1 of therapy (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Up to 2 years
Dose limiting toxicities	Will be assessed by NCI CTCAE v 5.	The first cycle of therapy (each cycle is 28 days)
Pharmacokinetic (PK) parameters: Maximum concentration	Will be assessed in plasma samples and will be determined by a validated hybridization enzyme-linked immunoassay (ELISA) method.	Cycle 1 day 1: Pre-dose, 30 minutes, 1 hour, 4-5 hours, 6-8 hours; cycle 1 day 2 at 24 hours (each cycle is 28 days)
PK parameters: Time to peak drug concentration	Will be assessed in plasma samples Will be assessed in plasma samples and will be determined by a validated hybridization ELISA method.	Cycle 1 day 1: Pre-dose, 30 minutes, 1 hour, 4-5 hours, 6-8 hours; cycle 1 day 2 at 24 hours (each cycle is 28 days)
PK parameters: Elimination half-life	Will be assessed in plasma samples Will be assessed in plasma samples Will be assessed in plasma samples and will be determined by a validated hybridization ELISA method.	Cycle 1 day 1: Pre-dose, 30 minutes, 1 hour, 4-5 hours, 6-8 hours; cycle 1 day 2 at 24 hours (each cycle is 28 days)
PK parameters: Clearance distribution	Will be assessed in plasma samples Will be assessed in plasma samples Will be assessed in plasma samples and will be determined by a validated hybridization ELISA method.	Cycle 1 day 1: Pre-dose, 30 minutes, 1 hour, 4-5 hours, 6-8 hours; cycle 1 day 2 at 24 hours (each cycle is 28 days)
PK parameters: Volume of distribution	Will be assessed in plasma samples Will be assessed in plasma samples Will be assessed in plasma samples and will be determined by a validated hybridization ELISA method.	Cycle 1 day 1: Pre-dose, 30 minutes, 1 hour, 4-5 hours, 6-8 hours; cycle 1 day 2 at 24 hours (each cycle is 28 days)
The antileukemic activity of imetelstat	Will be assessed by complete remission (CR)/CR with incomplete platelet counts (CRp)/CR with incomplete hematologic recovery (CRi) and rates of minimal residual disease negative response.	After up to two cycles of therapy (each cycle is 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics	Will characterize the pharmacodynamic properties of imetelstat in pediatric patients with refractory or second or greater relapse of AML, or first or greater relapse of MDS, or JMML	Up to 2 years
Telomerase activity	Telomerase activity will be assessed in peripheral blood mononuclear cells.	Cycle 1 day 1, pre-dose and cycle 1 day 2 at 24 hours (each cycle is 28 days)
Cytogenetic abnormalities	Compare baseline cytogenetic abnormalities vs. change of cytogenetic abnormalities after treatment	At baseline and after cycle 2 (each cycle is 28 days)
Mutational status	Compare baseline mutational status vs. change of mutational status after treatment	At baseline and after cycle 2 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Investigators: Principal Investigator: Alexandra M Stevens, Pediatric Early Phase Clinical Trial Network

Study record dates

Study Major Dates

• Study Start (Estimated): July 12, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: January 18, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence; Preleukemia; Leukemia, Myelomonocytic, Juvenile; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Dermatologic Agents; Micronutrients; Protein Kinase Inhibitors; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Antidotes; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Leucovorin; Calcium; Levoleucovorin; Fludarabine; Cytarabine; Methotrexate; Folic Acid; Calcium, Dietary; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Imetelstat; Motesanib diphosphate
• Other Study ID Numbers: PEPN2312 (Other Identifier: CTEP); UM1CA228823 (U.S. NIH Grant/Contract); NCI-2023-11026 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes