Combining Talazoparib with Chemotherapy for Relapsed Pediatric AML
A Phase I Protocol for Relapsed Pediatric AML to Determine the Safety and Efficacy of the PARP Inhibitor Talazoparib in Combination With Chemotherapy
This study is testing if a new combination of a drug called talazoparib with standard chemotherapy can help children and young adults with relapsed acute myeloid leukemia feel better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 34 (estimated) |
| Ages | N/A to 21 Years |
| Sex | All |
| Sponsor | Stanford University Academic / other |
| Drugs / interventions | gemtuzumab, chemotherapy, immunotherapy, radiation, prednisone |
| Locations | 9 sites (Phoenix, Arizona and 8 other locations) |
| Trial ID | NCT05101551 on ClinicalTrials.gov |
What this trial studies
This Phase 1, open-label, multicenter study evaluates the safety and tolerability of talazoparib in combination with conventional chemotherapy for children and young adults with relapsed acute myeloid leukemia (AML). The study involves a dose escalation phase to determine the maximum tolerated dose of talazoparib, topotecan, and gemcitabine, followed by a dose expansion cohort to gather preliminary efficacy data. The goal is to assess how well this combination can work in treating relapsed or refractory AML in pediatric patients.
Who should consider this trial
Good fit: Ideal candidates for this study are children and young adults aged 21 years or younger with relapsed or refractory acute myeloid leukemia.
Not a fit: Patients with acute myeloid leukemia who are not relapsed or refractory, or those who do not meet the specific eligibility criteria, may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new treatment option for pediatric patients with relapsed AML, potentially improving their outcomes.
How similar studies have performed: While the combination of PARP inhibitors with chemotherapy is a novel approach in pediatric AML, similar strategies in adult populations have shown promise, indicating potential for success in this demographic.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Aged ≤ 21 years.
2. 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:
1. Bone marrow specimen ≥ 5% leukemic blasts by flow, as assessed by Hematologics Inc.
2. 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
3. Rising MRD \> 0.1% by flow cytometry on ≥ 2 serial samples, as assessed by Hematologics Inc.
4. 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
3. \> 60 days has passed since hematopoietic stem cell transplant.
4. 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.
5. 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.
6. 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).
7. Lansky (subjects ≤ 16 years old) or Karnofsky (subjects \> 16 years old) score ≥ 50.
8. WBC ≤ 50,000/uL. This may be achieved using cytoreductive therapy such as hydroxyurea or low-dose cytarabine (up to 100 mg/m2/dose)
9. Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) for age.
10. AST/ALT ≤ 5 x ULN for age
11. Left ventricular ejection fraction ≥ 40% or ECHO shortening fraction ≥ 25%.
12. Estimated serum creatinine ≥ 60 mL/min/1.73m2
Exclusion Criteria:
1. Patients receiving or planning to receive ANY concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy or biologic therapy.
2. Patients with down syndrome.
3. Patients with Acute Promyelocytic leukemia (APL) or Juvenile Myelomonocytic Leukemia (JMML).
4. Patients with Bone Marrow Failure Syndrome.
5. Pregnant subjects or those unwilling to use an effective method of birth control.
6. Female subjects with infants who do NOT agree to abstain from breastfeeding.
7. Inability or unwillingness of legal guardian/representative to give written informed consent.
8. Patients with uncontrolled systemic fungal, bacterial, viral or other infection.
Where this trial is running
Phoenix, Arizona and 8 other locations
- Phoenix Children's Hospital — Phoenix, Arizona, United States (Recruiting)
- Arkansas Children's Hospital — Little Rock, Arkansas, United States (Recruiting)
- City of Hope — Duarte, California, United States (Recruiting)
- Stanford University — Stanford, California, United States (Recruiting)
- Cincinnati Children's Hospital — Cincinnati, Ohio, United States (Recruiting)
- Pennsylvania State University Hershey Medical Center — Hershey, Pennsylvania, United States (Recruiting)
- St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
- University of Utah — Salt Lake City, Utah, United States (Recruiting)
- University of Wisconsin Carbone Cancer Center — Madison, Wisconsin, United States (Recruiting)
Study contacts
- Principal investigator: Norman Lacayo, MD — Stanford Universiy
- Study coordinator: Stefania Chirita
- Email: schirita@stanford.edu
- Phone: (650)721-4087
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.