Recruiting PHASE1 Recurrent Childhood Acute Myeloid Leukemia

New treatment option for Recurrent Childhood Acute Myeloid Leukemia

Official title 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

ClinicalTrials.gov ID: NCT06247787

What this study is testing

What is Cytarabine?

Cytarabine is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for recurrent childhood acute myeloid leukemia.

Also referred to as .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: 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.

Phase 1: an early, usually small safety study

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 1 to 18

You may be able to join 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...
First or greater relapse of MDS
First or greater relapse of JMML

You likely can't join 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...
Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to...
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...
Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone...
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...

See the full eligibility criteria

Who can 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...
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...
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...
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...
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...
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...
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 (≥...
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...
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...
≥ 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...
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...
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...
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...
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 ≤...
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...
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

What rules you out

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...
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...
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

The study team makes the final eligibility decision.

Where it's taking place

Birmingham, Alabama, United States
Orange, California, United States
San Francisco, California, United States
Aurora, Colorado, United States
Washington D.C., District of Columbia, United States
Atlanta, Georgia, United States
Chicago, Illinois, United States
Indianapolis, Indiana, United States
Boston, Massachusetts, United States
Ann Arbor, Michigan, United States
Minneapolis, Minnesota, United States
St Louis, Missouri, United States
New York, New York, United States
Cincinnati, Ohio, United States
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
Memphis, Tennessee, United States
Houston, Texas, United States
Seattle, Washington, United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 1 year to 18 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Birmingham, Alabama, United States; Orange, California, United States; San Francisco, California, United States; Aurora, Colorado, United States; Washington D.C., District of Columbia, United States; Atlanta, Georgia, United States and 13 more location(s). Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.