Phase 2
N=25
Decitabine and Talazoparib in Untreated AML and R/R AML
Acute Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT02878785 ↗Enrolled (actual)
25
Serious AEs
100.0%
Results posted
Jun 2022
Primary outcome: Primary: Phase 1 - Dose Finding — 10; 15; 20; 20 mg/m^2
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Decitabine (Drug); talazoparib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Maryland, Baltimore
- Primary completion
- Jan 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1 - Dose Finding |
10; 15; 20; 20; 20; 20 | — |
Summary
The purpose of this study is to find the best way to combine a new chemotherapy drug with one that is already in use to treat AML. The new experimental drug is called talazoparib (also known as BMN-673), and it is not approved by the Federal Drug Administration (FDA). The FDA is allowing the use of talazoparib for the purposes of this study.
Decitabine is used to treat bone marrow diseases called myelodysplastic syndromes (MDS), as well as off label for AML.
Lab work suggests that talazoparib will increase the effects of decitabine in leukemia cells.
Investigators hope that treating patients with decitabine and talazoparib together will be more successful that treating patients with decitabine alone.
This study has two parts. The purpose of part one the study is to find out the best doses of decitabine and talazoparib to use when they are given together to treat AML. The purpose of part two is to see how well the drugs work together to treat AML.
All participants in the study will be treated with decitabine and talazoparib.
Part one of the study will include as few as two people and as many as 36 people to find the best dose levels of the study drugs. Part one will begin enrolling first. Part two of the study will not start until the Part one of the study is complete. Participants will be told which part of the study they may be enrolled in. Part two of the study may include as few as 79 people and as many as 135 people. Part two includes three separate arms. Participants enrolled in Part two of the study, will be assigned to one of the three arms below in order to test the success rate of the study drug dose determined by Part one:
* Arm A will enroll adult patients with AML who are thought not to be likely to tolerate or respond to standard chemotherapy;
* Arm B will enroll adult patients with AML that has not responded to previous treatment or has come back after responding to previous treatment;
* Arm C will enroll adult patients previously treated with a DNA methyltransferase inhibitor (decitabine, azacitidine or guadecitabine).
This is a multi-center study. Up to 171 people may take part in this study globally.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of AML based on 2008 WHO criteria. AML may be de novo, following a prior hematologic disorder, including MDS or Philadelphia chromosome-negative myeloproliferative neoplasm, and/or therapy-related.
- PHASES 1 AND 2: Patients with AML that has relapsed after, or is refractory to, first-line therapy, with or without subsequent additional therapy, and are currently considered unfit for, or unlikely to respond to, cytotoxic chemotherapy.
- PHASE 2 ONLY: Patients previously untreated for AML who are considered unfit for cytotoxic chemotherapy by virtue of performance status, comorbidities, advanced age and/or low likelihood of response based on disease characteristics, or who decline cytotoxic induction chemotherapy.
- Patients who have undergone autologous stem cell transplantation (autoSCT) are eligible provided that they are ≥ 4 weeks from stem cell infusion.
- Patients who have undergone allogeneic SCT (alloSCT) are eligible if they are ≥ 60 days from stem cell infusion, have no evidence of graft versus host disease (GVHD) > Grade 1, and are ≥ 2 weeks off all immunosuppressive therapy.
- Previous cytotoxic chemotherapy must have been completed at least 3 weeks and radiotherapy at least 2 weeks prior to Day 1 of treatment on the study, and all adverse events (excluding alopecia) due to agents administered more than 4 weeks earlier should have recovered to 50,000 blasts/μl. Hydroxyurea for blast count control is permitted before starting treatment, but must be stopped prior to starting treatment on the study. Patients will be withdrawn from the study if > 50,000 blasts/μl occur or recur > 14 days after starting treatment on the study.
- Active, uncontrolled infection. Patients with infection controlled with antibiotics are eligible.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per investigator's judgment would limit compliance with study requirements.
- Patients who are pregnant or nursing.
- Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks for antecedent malignancies prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or talazoparib.
- Known HIV infection.
HIV-positive patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Previous treatment with talazoparib.
Data sourced from ClinicalTrials.gov (NCT02878785). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.