NCT05101551 · Norman J. Lacayo
Study of Talazoparib in Combination With Chemotherapy in Relapsed Pediatric AML to Determine Safety and Efficacy
(PARPAML)
What this study is about
This is a Phase 1, open label, conducted at multiple hospitals, dose finding study with dose expansion intended to evaluate the safety and how well patients handle the treatment of talazoparib in combination with conventional chemotherapy.
View original scientific description
This is a Phase 1, open label, multicenter, dose finding study with dose expansion intended to evaluate the safety and tolerability of talazoparib in combination with conventional chemotherapy. Preliminary estimates of efficacy will be obtain through a dose expansion cohort receiving the maximum tolerated dose from the dose escalation phase of the study. This study aims to determine the safety of talazoparib in combination with conventional chemotherapy and to establish the maximum tolerated dose of all 3 drugs when given in combination. A preliminary estimate of efficacy through a dose expansion phase is a secondary aim.
Interventions
DRUG
Talazoparib
Talazoparib will be administered in escalating doses based on current dose level. * Dose Level 1: 400 µg/m2/dose once daily * Dose Level 2: 600 µg/m2/dose BID on Day 1, then daily on Days 2 to 5 * Dose Level 3: 600 µg/m2/dose BID on Day 1, then daily on Days 2 to 5 * Dose Level 4: 600 µg/m2/dose BID on Day 1, then daily on Days 2 to 5 * Dose Level 5: 600 ug/m2/dose BID on Day 1, then daily on Days 2 to 5 and 15 to19
DRUG
Topotecan
Administered IV route on Days 1 to 5 * Dose Level -2: 1 mg/m2/dose once daily by IV days 1 to 5 * Dose Level -1: 2 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 1: 2 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 2: 2 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 3: 3 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 4: 4 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 5: 4 mg/m2/dose once daily by IV days 1 to 5
DRUG
Gemcitabine
Single dose (IV) of gemcitabine on Day 1 of each 28 day cycle for 1 cycle. * Dose Level -2: 600 mg/m2/dose once daily by IV days 1 * Dose Level -1: 600 mg/m2/dose once daily by IV days 1 * Dose Level 1: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 2: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 3: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 4: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 5: 1200 mg/m2/dose once daily by IV days 1
Primary outcome measures
Dose limiting toxicity (DLT).
Time frame: 28 days after starting therapy (ie, single course of therapy).
Patient safety is assessed as dose limiting toxicity (DLT). The outcome is the number of DLT events. A DLT event is defined as: * Hematologic DLT - Failure to recover peripheral ANC to \> 200/µL or non-transfusion-dependent platelets to \> 20,000/µL by Day 43 from the start of Cycle 1 of chemotherapy will be considered a DLT, unless the delay in count recovery is due to another identifiable factor * Non-Hematologic DLT-Any ≥ Grade 4 non-hematological organ toxicity, including Hy's Law case is a DLT with the following exceptions: * Grade 4 infection or fever ≤ 7 days in duration. * Grade 4 electrolyte or laboratory abnormalities correctable with supportive therapy or that resolve to \< Grade 3 within 72 hours. * Grade 4 elevation in hepatic transaminases that resolves to ≤ Grade 2 within 7 days. * Grade 4 tumor lysis syndrome must resolve in ≤ 7 days without evidence of end-organ damage.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Aged ≤ 21 years.
- Acute myeloid leukemia (AML) OR acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia), specified as either refractory (persistent leukemia after at least 2 courses of induction chemotherapy) or relapsed, and further defined as any one of the criteria below:
- Bone marrow specimen ≥ 5% leukemic blasts by flow, as assessed by Hematologics Inc.
- A single bone marrow specimen with at least 2 tests demonstrates ≥ 1% leukemic blasts by flow cytometry (as assessed by Hematologics Inc), AND at least one of the following:
- Karyotypic abnormality with at least 1 metaphase similar or identical to diagnosis
- FISH abnormality identical to one present at diagnosis
- PCR or NGS-based demonstration of leukemogenic lesion identical to diagnosis
- Rising MRD \> 0.1% by flow cytometry on ≥ 2 serial samples, as assessed by Hematologics Inc.
- If an adequate bone marrow sample is not obtained, subjects may be enrolled if there is unequivocal evidence of leukemia based on ≥ 5% blasts in the peripheral blood
- \> 60 days has passed since hematopoietic stem cell transplant.
- Patients who have undergone previous allogeneic stem cell transplantation who are otherwise eligible must also be without evidence of any active graft versus host disease (GVHD), and off calcineurin inhibitors for at least 28 days (four weeks) prior to therapy. A physiologic dose of prednisone up to 3 mg/m2 (and a maximum of 7.5 mg) or equivalent other steroid dose is allowable.
- A minimum of 14 days has passed since completion of myelosuppressive therapy or gemtuzumab ozogamicin and all nonhematologic toxicities have resolved to Grade 0 or 1.
- A minimum of 24 hours has elapsed since the patient has completed any low-dose or non-myelosuppressive therapy (e.g., hydroxyurea or low-dose cytarabine (up to 100 mg/m2).
- Lansky (subjects ≤ 16 years old) or Karnofsky (subjects \> 16 years old) score ≥ 50.
- WBC ≤ 50,000/uL. This may be achieved using cytoreductive therapy such as hydroxyurea or low-dose cytarabine (up to 100 mg/m2/dose)
- Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) for age.
- AST/ALT ≤ 5 x ULN for age
- Left ventricular ejection fraction ≥ 40% or ECHO shortening fraction ≥ 25%.
- Estimated serum creatinine ≥ 60 mL/min/1.73m2
Exclusion criteria
- Patients receiving or planning to receive ANY concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy or biologic therapy.
- Patients with down syndrome.
- Patients with Acute Promyelocytic leukemia (APL) or Juvenile Myelomonocytic Leukemia (JMML).
- Patients with Bone Marrow Failure Syndrome.
- Pregnant subjects or those unwilling to use an effective method of birth control.
- Female subjects with infants who do NOT agree to abstain from breastfeeding.
- Inability or unwillingness of legal guardian/representative to give written informed consent.
- Patients with uncontrolled systemic fungal, bacterial, viral or other infection.
Where
- Phoenix, Arizona
- Little Rock, Arkansas
- Duarte, California
- Stanford, California
- Cincinnati, Ohio
- Hershey, Pennsylvania
- Memphis, Tennessee
- Salt Lake City, Utah
- Madison, Wisconsin
Collaborators
Gateway for Cancer Research
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 22, 2026 · Source of record for eligibility and locations