NCT05101551

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P50-P75 for phase_1

Timeline
10mo left

Started Feb 2023

Longer than P75 for phase_1

Geographic Reach
1 country

9 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress79%
Feb 2023Apr 2027

First Submitted

Initial submission to the registry

October 28, 2021

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 1, 2021

Completed
1.3 years until next milestone

Study Start

First participant enrolled

February 23, 2023

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Last Updated

April 22, 2026

Status Verified

April 1, 2026

Enrollment Period

4.1 years

First QC Date

October 28, 2021

Last Update Submit

April 21, 2026

Conditions

Acute Myeloid Leukemia

Keywords

PARP Inhibitor

Outcome Measures

Primary Outcomes (1)

  • Dose limiting toxicity (DLT).

    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.

    28 days after starting therapy (ie, single course of therapy).

Secondary Outcomes (1)

  • Objective Response (OR)

    28 days

Study Arms (1)

Talazoparib with topotecan and gemcitabine

EXPERIMENTAL

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.

Drug: TalazoparibDrug: TopotecanDrug: Gemcitabine

Interventions

TalazoparibDRUG

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

Also known as: Talzenna
Talazoparib with topotecan and gemcitabine
TopotecanDRUG

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

Also known as: Hycamtin
Talazoparib with topotecan and gemcitabine
GemcitabineDRUG

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

Also known as: Gemzar, Infugem
Talazoparib with topotecan and gemcitabine

Eligibility Criteria

AgeUp to 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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)
  • +4 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Pennsylvania State University Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84108, United States

RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

talazoparibTopotecanGemcitabine

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Norman Lacayo, MD

    Stanford Universiy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefania Chirita

CONTACT

(650)721-4087schirita@stanford.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Instructor Pediatrics - Hematology/Oncology

Study Record Dates

First Submitted

October 28, 2021

First Posted

November 1, 2021

Study Start

February 23, 2023

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

April 1, 2027

Last Updated

April 22, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(9)