Decitabine and Talazoparib in Untreated AML and R/R AML (1565GCC)
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|ClinicalTrials.gov Identifier: NCT02878785|
Recruitment Status : Recruiting
First Posted : August 25, 2016
Last Update Posted : November 4, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Decitabine Drug: talazoparib||Phase 1 Phase 2|
In this clinical trial, invvestigators combine decitabine and talazoparib in the treatment of patients with AML. Decitabine will be given in the established regimen of IV daily dosing for 5 days every 28 days. Talazoparib will be initiated orally daily on a continuous basis, beginning on Day 1 of Course 1. In this phase 1 trial, decitabine and talazoparib will be tested at 3 and 4 dose levels, respectively, yielding up to 6 combinations. Doses will be escalated based on tolerability using a 'classic' 3+3 design. Once the MTD for decitabine combined with 0.25 mg talazoparib is established, the dose of talazoparib will be escalated with the dose of decitabine kept fixed at the provisional MTD dose. There is no further stepping up or down of the drugs in the combination.
The regimen for phase 2 testing will be chosen based on tolerability, but also based on available pharmacodynamic and efficacy data. In phase 2, the selected combination regimen will be studied for efficacy.
Each patient will be treated until occurrence of either unacceptable toxicity or disease progression. Bone marrow aspirate and biopsy will be performed on approximately day 28 of each treatment course unless circulating blasts persist in the peripheral blood, until documentation of CR or CRi. Bone marrow aspirate and biopsy will then be repeated at time of clinical concern for disease progression.
In Phase 1, the clinical trial will enroll patients with relapsed and refractory AML in order to test the novel combination initially in patients with less favorable outcomes with decitabine alone. This is being done to avoid the possibility of compromising the outcomes of untreated patients, who have up to a 40% response rate to 5-day decitabine as a single agent, in the unlikely possibility that the combination is inferior. The regimen will then also be tested in previously untreated AML patients unfit for chemotherapy in phase 2.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||171 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Phase 1/2 Study of Combination Therapy w/ DNA Methyltransferase Inhibitor Decitabine & Poly ADP Ribose Polymerase Inhibitor Talazoparib for Untreated AML in Adults Unfit for Cytotoxic Chemotherapy or R/R AML|
|Actual Study Start Date :||August 2016|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2022|
Experimental: Decitabine and Talazoparib Combo
Decitabine by IV daily for 5 days every 28 days. Talazoparib orally daily days 1-28.
The 'outer layer' of this nested dose escalation trial will escalate the dose of the two drugs by sequentially going through dose levels 1-6 in the table found in the protocol. The standard algorithm of the 3+3 design will be applied.
Decitabine by IV daily for 5 days every 28 days. Talazoparib orally daily days 1-28. Phase 2 doses will be determined based on data from Phase 1.
DNA methyltransferase inhibitor
Other Name: dacogen
poly ADP ribose polymerase (PARP) inhibitor
Other Name: BMN673; MDV3800
- Phase 1 - Dose finding [ Time Frame: Cycle length = 28 days ]To determine the recommended Phase 2 doses based on numbers of participants with treatment-related adverse events, evaluated according to Version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE).
- Phase 2 - Efficacy [ Time Frame: Evaluated every 28 days through study completion, an average of 1 year. ]Number of participants achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi), defined by the Cheson criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02878785
|Contact: Sunita Philip, MPH, CCRPfirstname.lastname@example.org|
|Contact: Gary Saumemail@example.com|
|United States, Maryland|
|University of Maryland Greenebaum Comprehensive Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Sunita Philip, MPH, CCRP 410-328-8199 firstname.lastname@example.org|
|Contact: Gary Saum 410-328-1180 email@example.com|
|Principal Investigator: Maria Baer, MD|
|Principal Investigator:||Maria Baer, MD||University of Maryland, College Park|