Talazoparib for Cohesin-Mutated AML and MDS With Excess Blasts

NCT03974217 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-152
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is testing if Talazoparib is an effective treatment for patients with AML and MDS that have a mutation in the cohesin complex.

Conditions

Leukemia

Keywords

Leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with ≥ 50% leukemic blast reduction with Talazoparib monotherapy as a marker of anti-leukemic activity.

  The investigators will measure the reduction in bone marrow blast percentage before and after therapy at the end of cycle 1 and determine the proportion of patients who have a 50% or greater reduction.

  1 year

Secondary Outcomes (4)

• Number of participants with reduction in blasts over time on study treatment

  1 year

• To determine the number of participants with reduction in mutation burden

  1 year

• Determine overall response rate in study participants

  1 year

• To determine the incidence of treatment-emergent adverse events

  1 year

Study Arms (2)

Talazoparib Part I

EXPERIMENTAL

* Talazoparib is administered orally on a daily basis * Hydroxyurea is allowed for up to two cycles per institutional guidelines

Drug: Talazoparib

Talazoparib + Decitabine Part II

EXPERIMENTAL

* Talazoparib is administered orally on a daily basis * Hydroxyurea is allowed for up to two cycles per institutional guidelines * Decitabine on days 1-5

Drug: Talazoparib; Drug: Decitabine

Interventions

Talazoparib DRUG

Talazoparib is a drug that stops the activity of a protein called poly (adenosine diphosphate \[ADP\]-ribose) polymerase or PARP. PARP is involved in repairing damage to the DNA within the cells. When PARP is turned off by Talazoparib in cancer cells, DNA damage cannot be repaired and leads to the death of the cancer cells.

Also known as: Talzenna

Talazoparib + Decitabine Part II; Talazoparib Part I

Decitabine DRUG

Decitabine is a drug that is meant to inhibit DNA methylation to restore normal functions to genes and helps to support normal cell production in the bone marrow and the death of abnormal bone marrow cells.

Also known as: Dacogen

Talazoparib + Decitabine Part II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be considered ineligible to receive intensive chemotherapy by treating investigator and must have a diagnosis of one of the following:
• Secondary AML (can be untreated secondary AML if previously treated for MDS, MDS/MPN, or any MPN with any anti-leukemic therapy; but cannot be recommended to receive any available approved AML therapy)
• Relapsed or refractory AML or relapsed/refractory AML without available approved AML therapy including transplantation or intensive chemotherapy or targetable lesion such as FLT3 or IDH1/IDH2
• Relapsed or Refractory MDS with a minimum of at least 4 cycles of decitabine or 6 cycles of azacitidine or sooner if they experience intolerance/progression/relapse while on HMA-based therapy.
• Persistent MDS/AML disease despite receiving at least 2 cycles of hypomethylating agent and venetoclax
• Previously untreated higher risk MDS by IPSS-R (\>3.5) who require treatment per treating investigator. Exceptions: Patients recommended for immediate transplant and have a donor ready or patients recommend for intensive chemotherapy
• Participants must have measurable disease defined as 5% or more blasts (blood or bone marrow).
• Age 18 years and older.
• ECOG performance status ≤2 (see Appendix A)
• Participants must have normal organ function as defined below:
• total bilirubin ≤ 2.5 × institutional upper limit of normal (unless considered to be secondary to leukemia)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal (unless considered to be secondary to leukemia)
• creatinine clearance ≥ 60 mL/min/1.73 m2
• Documented pathogenic mutation in cohesin complex including a mutation in STAG2, SMC1A, RAD21, PDS5B, or SMC3 gene from a CLIA-approved test (local testing allowed; will be centrally confirmed). Patient must have a minimum VAF of 5%. Historical results from (up to 3 months prior to study registration) allowed for treatment start on study if no recent disease-modifying agent was received since testing.
• The effects of Talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitor agents are suspected to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study participation, and 4 months after completion of Talazoparib administration.

You may not qualify if:

• Participants receiving any leukemia-directed chemotherapy within 2 weeks prior to study registration or those who have not recovered from adverse events (to at least grade 1 with exception of alopecia) due to chemotherapy administered more than 2 weeks earlier. Exceptions: hydroxyurea and prior palliative radiotherapy is permitted if completed within 5 days prior to study registration and patient has no clinically significant toxicities such as mucositis or esophagitis.
• No prior PARP inhibitor for any indication.
• No limitations to prior MDS/AML therapy including HMA (azacitidine or decitabine). If a patient is post allogeneic hematopoietic stem cell transplant, he/she must be \> 2 months from day of donor cell infusion to date of study registration. They must be off immunosuppression therapy for at least 14 days prior to registration (topical steroids are permitted).
• Participants who are receiving any other investigational agents.
• Participants with known CNS leukemia.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise safety assessment, in the judgement of the investigator.
• Pregnant women are excluded from this study because Talazoparib is a PARP inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Talazoparib, breastfeeding should be discontinued if the mother is treated with Talazoparib. These potential risks may also apply to other agents used in this study.
• Patient has known active HIV, HCV or HBV.
• Patients with prior malignancy are eligible however patient must either be in remission from prior malignancy OR have inactive (note: meaning they do not require treatment) and asymptomatic disease. Maintenance therapy such as hormone therapy is allowed

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia

Interventions

talazoparib; Decitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jacqueline Garcia, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: June 4, 2019
• Study Start: August 1, 2019
• Primary Completion: April 3, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)