RECRUITING

Study of Talazoparib in Combination With Chemotherapy in Relapsed Pediatric AML to Determine Safety and Efficacy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

A Phase I Protocol for Relapsed Pediatric AML to Determine the Safety and Efficacy of the PARP Inhibitor Talazoparib in Combination With Chemotherapy

Quick Facts

Study Start:2023-02-23

Study Completion:2026-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05101551

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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	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.

Inclusion Criteria

Exclusion 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

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.

Contacts and Locations

Study Contact

Sophia Brodsky

CONTACT

(650)721-4087

sophia.brodsky@stanford.edu

Principal Investigator

Jennifer L Kamens, MD

PRINCIPAL_INVESTIGATOR

Stanford Universiy

Study Locations (Sites)

Phoenix Children's Hospital

Phoenix, Arizona, 85016

United States

Arkansas Children's Hospital

Little Rock, Arkansas, 72202

United States

City of Hope

Duarte, California, 91010

United States

Stanford University

Stanford, California, 94305

United States

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229

United States

Pennsylvania State University Hershey Medical Center

Hershey, Pennsylvania, 17033-0850

United States

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

United States

University of Utah

Salt Lake City, Utah, 84108

United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Norman J. Lacayo

Jennifer L Kamens, MD, PRINCIPAL_INVESTIGATOR, Stanford Universiy

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-02-23

Study Completion Date2026-03

Study Record Updates

Study Start Date2023-02-23

Study Completion Date2026-03

Terms related to this study

Keywords Provided by Researchers

PARP Inhibitor

Additional Relevant MeSH Terms

Acute Myeloid Leukemia