PARPAML: Relapsed Pediatric AML to Determine the Safety and Efficacy of the PARP Inhibitor Talazoparib in Combination With Conventional Chemotherapy

Sponsor
Stanford University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05101551
Collaborator
(none)
50
1
1
16
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Nov 1, 2022
Anticipated Primary Completion Date :
Mar 1, 2024
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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 each 28 day cycle for 1 cycle.

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 19

Drug: Topotecan
Administered IV route on Days 1 to 5. Recommended dose based on this study is 4 mg/m2/dose.

Drug: Gemcitabine
Single dose (IV) of gemcitabine on Day 1 of each 28 day cycle for 1 cycle.

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicity (DLT). [28 days28 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 a Grade 3, 4, or 5 event, with the exception of following Grade 3 4 events. Infection and/or fever Elevation in liver enzymes Changes in blood electrolyte levels for > 24 hours. Changes in blood sugar for > 24 hours. Fatigue and/or nausea (Grade 3 only). Vomiting and/or diarrhea (Grade 3 only) ≤ 7 days Hypotension associated with sepsis or infusion reaction Mucositis (Grade 3 only) ≤ 14 days Anorexia (Grade 3 only) Hypertension (Grade 3 only) Enterocolitis, typhlitis, or colitis (Grade 3 only) Gastric hemorrhage, gastric ulcer, gastritis, and/or upper GI bleed (Grade 3 only) Glucose intolerance (Grade 3 only) Leukoencephalopathy and/or seizures (Grade 3 only) Any Grade 3 event secondary to an infectious process or thrombocytopenia Other Grade 3 events resolving ≤ 48 hours

Secondary Outcome Measures

  1. Objective Response (OR) [28 days.]

    Objective response (OR) is a collective term representing all participants that achieve a complete response or partial response, and will be assessed for all participants treated at the maximum tolerated dose, including the Dose Expansion cohort. Response will be defined as below: Complete remission (CR) or complete remission without hematologic recovery (CRi): Bone marrow MRD <0.1% by flow cytometry Complete response (CRM) or without hematologic recovery (CRMi): Bone marrow MRD 0.1 to 5% by flow cytometry Partial response (PR): A decrease of at least 50% in the percentage of morphologic blasts and 5% to 25% blasts by flow cytometry No response (NR): No change in clinical or laboratory status Progressive Disease (PD): Deterioration of initial disease status The outcome will be reported as the number of participants that achieve OR, ie, a CR, CRi, CRM, CRMi, or PR. The outcome is a number without dispersioni.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
    1. AML or acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia) and have (a) refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy, OR (b)relapsed leukemia, defined as ≥ 1% blasts in the bone marrow OR rising MRD by flow cytometry on two or more serial samples.

If an adequate bone marrow sample cannot be obtained, subjects may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood.

Exclusion Criteria:
    1. Uncontrolled infection. Infections controlled on concurrent anti microbial agents are acceptable, and anti microbial prophylaxis per institutional guidelines are acceptable.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Stanford University Stanford California United States 94305

Sponsors and Collaborators

  • Stanford University

Investigators

  • Principal Investigator: Jennifer L Kamens, MD, Stanford Universiy

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Stanford University
ClinicalTrials.gov Identifier:
NCT05101551
Other Study ID Numbers:
  • IRB 59562
  • PEDSHEMAML0008
First Posted:
Nov 1, 2021
Last Update Posted:
Jun 15, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Stanford University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 15, 2022