AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1PARPAMLNCT05101551

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

A Phase 1 study testing Talazoparib, Topotecan and Gemcitabine in people with Acute Myeloid Leukemia, run by Norman J. Lacayo at 9 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Talazoparib, Topotecan and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
9 sitesUnited States
Study dates
23 Feb 2023to Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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)
  • Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) for age.
  • AST/ALT ≤ 5 x ULN for age
  • Left ventricular ejection fraction ≥ 40% or ECHO shortening fraction ≥ 25%.
  • Estimated serum creatinine ≥ 60 mL/min/1.73m2

Who cannot join

  • 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.

Trial locations and contacts

9 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Stefania Chirita contact

(650)721-4087

schirita@stanford.edu

9 sites in 1 country

United States9 sites, 9 recruiting

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

    Jennifer Kamens, MD, 215-589-8456, jennifer.kamens@cchmc.org

    Jennifer Kamens, MD

    Recruiting

  • City of Hope

    Duarte, California, 91010

    Lindsey Murphy, MD, 626-218-0948, lmurphy@coh.org

    Lindsey Murphy, MD

    Recruiting

  • Pennsylvania State University Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

    Valerie Brown, MD, PhD, 717-531-6012, vbrown1@hmc.psu.edu

    Valerie Brown, MD, PhD

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

    Kevin Bielamowicz, MD, 501-364-4405, kjbielamowicz2@uams.edu

    Kevin J Bielamowicz, MD

    Recruiting

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

    Pediatric HemOnc Main Line, 608-263-6200, PedsHemOncResearch@g-groups.wisc.edu

    Cancer Connect, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Recruiting

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

    Seth Karol, MD, 901-595-1617, seth.karol@STJUDE.org

    Seth Karol, MD

    Recruiting

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

    Chris Oless, RN, 602-933-0920, coless@phoenixchildrens.com

    Laura Retson, DO

    Recruiting

  • University of Utah

    Salt Lake City, Utah, 84108

    Spencer Mangum, MD, 801-662-4700, Spencer.Mangum@hsc.utah.edu

    Spencer Mangum, MD

    Recruiting

  • Stanford University

    Stanford, California, 94305

    Ankita Amberkar, BS, (650)391-5318, ankitaamberkar@stanford.edu

    Norman Lacayo

    Recruiting

Other trials in United States

About this study

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

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.

Being tested
Talazoparib, Topotecan, Gemcitabine
Keywords
PARP Inhibitor
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TalazoparibDrug

    Also called Talzenna

    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

  • TopotecanDrug

    Also called Hycamtin

    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

  • GemcitabineDrug

    Also called Gemzar, Infugem

    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
Study groups in NCT05101551
Study groupRoleWhat they receive
Talazoparib with topotecan and gemcitabineExperimentalTalazoparib 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.
Receives: Drug: Talazoparib; Drug: Topotecan; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (1)

  1. Objective Response (OR)

    Objective response includes all participants that achieve complete or partial response, and assessed for all participants treated at the maximum tolerated dose.

    • Complete remission: Bone marrow MRD < 5% by flow cytometry, ANC ≥ 500/μL AND platelets ≥ 50,000/μL,without transfusions,No extramedullary disease
    • Complete remission without hematologic recovery: Bone marrow MRD < 5% by flow cytometry, One of ANC ≥ 500/μL OR platelets ≥ 50,000/μL,without transfusions, No extramedullary disease
    • Partial response: Decrease of at least 50% of blasts by MRD and ≥ 5% to 25% blasts by flow cytometry.Enrolled patients with fewer than 5% blasts by MRD are not evaluable for PR.
    • No response: No change in clinical or laboratory status.For patients with < 5% of blasts at enrollment, no response is defined as failure to achieve MRD negative CR or MRD negative CRi.
    • Progressive Disease: Deterioration of initial disease status
    • MRD negative: < 0.05% of leukemic blasts by flow cytometry.

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2021
  2. Study start23 Feb 2023
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05101551
Sponsor's protocol ID
IRB-66573
Other IDs
PEDSHEMAML0008, POE22-01, Pro00060706
Acronym
PARPAML
Status last verified
Apr 2026
First submitted
28 Oct 2021
Last updated
22 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Talazoparib, Topotecan and Gemcitabine in people with Acute Myeloid Leukemia, run by Norman J. Lacayo at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Stefania Chirita ((650)721-4087, schirita@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (DLT). (time frame: 28 days after starting therapy (ie, single course of therapy).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05101551.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in