LeukemiaPhase 1NCT03974217
Talazoparib for Cohesin-Mutated AML and MDS With Excess Blasts
A Phase 1 study testing Talazoparib and Decitabine in people with Leukemia, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- Talazoparib and Decitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Aug 2019to 1 Jan 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 17Show fewer
- 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.
- For women of child bearing potential only, must have a negative urine or serum pregnancy test.
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Pilot Proof-of-Concept Study of Talazoparib-Based Therapy for Cohesin-Mutated AML and MDS With Excess Blasts
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.
Read the detailed description
This research study is a Pilot Study, which is the first time investigators are examining this study drug for a selected subgroup of patients with AML and MDS whose disease features a mutation in the cohesin complex.
The FDA (the U.S. Food and Drug Administration) has approved Talazoparib as a treatment for certain kinds of breast cancer. It is not currently approved for treating your disease.
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 your cells. DNA is the set of instructions found within all of your cells that tells them how to behave. The DNA is damaged all the time by things around in the environment, and is repaired by several different methods, one of which uses PARP. When PARP is turned off by Talazoparib in the normal cells, other methods can still work to repair damage to DNA. However, in some cancer cells these other methods are broken and cannot be used. When PARP is turned off by Talazoparib in these cancer cells, DNA damage cannot be repaired and leads to the death of the cancer cells. Talazoparib is a drug that is safe and active in breast cancer and gynecologic cancers. However, there were no responses among 33 unselected patients with hematologic malignancies, including 21 with AML (acute myeloid leukemia) and 4 with MDS (myelodysplastic syndrome), when they received treatment with Talazoparib by itself. It is not known if there were any patients with cohesin-mutations that were on the clinical trial (these mutations are rare).
In this research study, the investigators are testing if Talazoparib is an effective treatment for patients with AML and MDS that have a mutation in the cohesin complex. The cohesin complex is made up of a group of proteins that are critical for normal DNA replication activity. Mutations in the cohesin complex occur in patients with MDS/AML and may represent a new therapeutic target. In a chemical screen experiment in a Dana-Farber Cancer Institute laboratory, the investigators found that leukemia cells featuring a mutated cohesin complex were sensitive to Talazoparib (meaning the leukemia cells went away after treatment with Talazoparib) by a mechanism called synthetic lethality (this means that the lab experiments showed that leukemia cells with a mutation in cohesin were dependent on PARP activity to survive; when inhibiting PARP with a PARP inhibitor like Talazoparib, the leukemia cells died). The investigators thus identified Talazoparib to be a possible treatment for actual patients with MDS or AML that have a mutation in cohesin complex.
- Conditions
- Leukemia
- Being tested
- Talazoparib, Decitabine
- Keywords
- Leukemia
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TalazoparibDrug
Also called Talzenna
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.
DecitabineDrug
Also called Dacogen
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.
| Study group | Role | What they receive |
|---|---|---|
| Talazoparib Part I | Experimental | * Talazoparib is administered orally on a daily basis
* Hydroxyurea is allowed for up to two cycles per institutional guidelines Receives: 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 Receives: Drug: Talazoparib; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (4)
Number of participants with reduction in blasts over time on study treatment
The investigators will measure the changes in bone marrow blast percentage at day +15, end of cycle 1, end of cycle 2 and every other cycle to determine the best response to talazoparib.
Measured: 1 year
To determine the number of participants with reduction in mutation burden
Using next-generation sequencing techniques, the investigators will measure for quantitative changes in variant allele frequency of the cohesin mutation while on talazoparib and determine if mutant VAF reduction correlates with blast reduction
Measured: 1 year
Determine overall response rate in study participants
The investigators will determine the best disease response according to IWG response criteria for MDS and ELN response criteria for AML
Measured: 1 year
To determine the incidence of treatment-emergent adverse events
The investigators will capture the AEs on and attribution to characterize the safety and toxicity profile of talazoparib in patients with AML or MDS
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start1 Aug 2019
- Primary completion3 Apr 2025
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Jacqueline Garcia, MD, Dana-Farber Cancer Institute
- Investigators
- Jacqueline Garcia, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03974217
- Sponsor's protocol ID
- 19-152
- Status last verified
- Jan 2026
- First submitted
- 22 May 2019
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Proof-of-Concept Study of Talazoparib-Based Therapy for Cohesin-Mutated AML and MDS With Excess Blasts
- ClinicalTrials.gov ID
- NCT03974217
- Acronym / sponsor ID
- 19-152
- Conditions
- Leukemia
- Keywords
- Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 3 Apr 2025 (actual)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 4 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This research study is a Pilot Study, which is the first time investigators are examining this study drug for a selected subgroup of patients with AML and MDS whose disease features a mutation in the cohesin complex.
The FDA (the U.S. Food and Drug Administration) has approved Talazoparib as a treatment for certain kinds of breast cancer. It is not currently approved for treating your disease.
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 your cells. DNA is the set of instructions found within all of your cells that tells them how to behave. The DNA is damaged all the time by things around in the environment, and is repaired by several different methods, one of which uses PARP. When PARP is turned off by Talazoparib in the normal cells, other methods can still work to repair damage to DNA. However, in some cancer cells these other methods are broken and cannot be used. When PARP is turned off by Talazoparib in these cancer cells, DNA damage cannot be repaired and leads to the death of the cancer cells. Talazoparib is a drug that is safe and active in breast cancer and gynecologic cancers. However, there were no responses among 33 unselected patients with hematologic malignancies, including 21 with AML (acute myeloid leukemia) and 4 with MDS (myelodysplastic syndrome), when they received treatment with Talazoparib by itself. It is not known if there were any patients with cohesin-mutations that were on the clinical trial (these mutations are rare).
In this research study, the investigators are testing if Talazoparib is an effective treatment for patients with AML and MDS that have a mutation in the cohesin complex. The cohesin complex is made up of a group of proteins that are critical for normal DNA replication activity. Mutations in the cohesin complex occur in patients with MDS/AML and may represent a new therapeutic target. In a chemical screen experiment in a Dana-Farber Cancer Institute laboratory, the investigators found that leukemia cells featuring a mutated cohesin complex were sensitive to Talazoparib (meaning the leukemia cells went away after treatment with Talazoparib) by a mechanism called synthetic lethality (this means that the lab experiments showed that leukemia cells with a mutation in cohesin were dependent on PARP activity to survive; when inhibiting PARP with a PARP inhibitor like Talazoparib, the leukemia cells died). The investigators thus identified Talazoparib to be a possible treatment for actual patients with MDS or AML that have a mutation in cohesin complex.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Talazoparib Part I | Experimental | Drug: Talazoparib* Talazoparib is administered orally on a daily basis * Hydroxyurea is allowed for up to two cycles per institutional guidelines |
| Talazoparib + Decitabine Part II | Experimental | Drug: Talazoparib, Drug: Decitabine* Talazoparib is administered orally on a daily basis * Hydroxyurea is allowed for up to two cycles per institutional guidelines * Decitabine on days 1-5 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Participants must be considered ineligible to receive intensive chemotherapy by treating investigator and must have a diagnosis of one of the following:
- 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:
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TalazoparibAlso: TalzennaTalazoparib 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. | Drug | Talazoparib + Decitabine Part II, Talazoparib Part I |
| DecitabineAlso: DacogenDecitabine 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. | Drug | Talazoparib + Decitabine Part II |
Primary outcome
Proportion of participants with ≥ 50% leukemic blast reduction with Talazoparib monotherapy as a marker of anti-leukemic activity.
Time frame: 1 year
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.
4 secondary outcomes
Number of participants with reduction in blasts over time on study treatment
Time frame: 1 year
To determine the number of participants with reduction in mutation burden
Time frame: 1 year
Determine overall response rate in study participants
Time frame: 1 year
To determine the incidence of treatment-emergent adverse events
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacqueline Garcia, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Talazoparib and Decitabine in people with Leukemia, run by Dana-Farber Cancer Institute at 2 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 17 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with ≥ 50% leukemic blast reduction with Talazoparib monotherapy as a marker of anti-leukemic activity. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Feb 2026.