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

NCT ID: NCT05101551

Last Updated: 2025-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-23

Study Completion Date

2026-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Talazoparib with topotecan and gemcitabine

Talazoparib will be administered orally on Days 1 to 5 concurrently with topotecan and a single dose of gemcitabine on Day 1 of 28 day cycle for 1 or 2 cycles. Subjects on dose level 5 will receive an additional 5 day treatment course of talazoparib on days 15-19.

Group Type EXPERIMENTAL

Talazoparib

Intervention Type DRUG

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

Topotecan

Intervention Type DRUG

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

Gemcitabine

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Talzenna Hycamtin Gemzar Infugem

Eligibility Criteria

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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.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gateway for Cancer Research

OTHER

Sponsor Role collaborator

Norman J. Lacayo

OTHER

Sponsor Role lead

Responsible Party

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Norman J. Lacayo

Instructor Pediatrics - Hematology/Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Norman Lacayo, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford Universiy

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

City of Hope

Duarte, California, United States

Site Status RECRUITING

Stanford University

Stanford, California, United States

Site Status RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status RECRUITING

Pennsylvania State University Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Stefania Chirita

Role: CONTACT

(650)721-4087

Facility Contacts

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Chris Oless, RN

Role: primary

602-933-0920

Kevin Bielamowicz, MD

Role: primary

501-364-4405

Lindsey Murphy, MD

Role: primary

626-218-0948

Stefania Chirita

Role: primary

650-721-4087

Jennifer Kamens, MD

Role: primary

215-589-8456

Valerie Brown, MD, PhD

Role: primary

717-531-6012

Seth Karol, MD

Role: primary

901-595-1617

Spencer Mangum, MD

Role: primary

801-662-4700

Pediatric HemOnc Main Line

Role: primary

608-263-6200

Cancer Connect

Role: backup

800-622-8922

Other Identifiers

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PEDSHEMAML0008

Identifier Type: OTHER

Identifier Source: secondary_id

POE22-01

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00060706

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-66573

Identifier Type: -

Identifier Source: org_study_id

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