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About
The purpose of the Phase 1b dose finding phase is to determine the safety, tolerability, and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of TAK-659 in participants with relapsed or refractory AML. The purpose of the Phase 2 expansion phase is to evaluate preliminary efficacy of TAK-659 in relapsed or refractory AML as measured by overall response rate (ORR).
Full description
The drug being tested in this study is TAK-659. TAK-659 is being tested to treat people who have relapsed or refractory acute myelogenous leukemia (AML). This study will be conducted in 2 phases. The first phase will determine a safe and well-tolerated dose of TAK-659 to be used in the second phase, and the second phase will look at response to treatment in people who take TAK-659.
The study will enroll approximately 106 participants (approximately 40 in the first phase and 66 in the second phase). There will be two separate cohorts during Phase 2 portion of the study, one for participants with FLT-3 internal tandem duplication (ITD) mutations and the other for FLT-3 wild-type participants.
Phase 1b:
• TAK-659 60 milligram (mg) tablet starting dose escalated in 20 mg or higher increments to a maximum tolerated dose or RP2D
Phase 2:
• TAK-659 tablet at the maximum tolerated dose or RP2D determined in Phase 1b.
All participants will be asked to take their prescribed tablets at the same time each day throughout the study.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 24 months (12 months of treatment and 12 months of follow up) unless the treating physician believes the participant would continue to derive benefit from the study drug.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Male or female participants 18 years or older.
Must have a histopathologically documented diagnosis of primary or secondary AML (excluding acute promyelocytic leukemia), as defined by World Health Organization (WHO) criteria (Jaffe et al, 2001), for whom no standard therapies are anticipated to result in a durable remission according to the clinical judgment of the principal investigator, or who refuses standard therapies (phase 1b and 2).
Participants for the phase 2 portion of the study must, in addition, meet the following:
o Must be refractory to or relapsed after no more than 2 prior chemotherapy regimens. Re-induction with the same regimen or stem cell transplant will not be considered a separate regimen.
Eastern Cooperative Oncology Group performance status of 0 to 1.
Female participants who:
Male participants, even if surgically sterilized (that is, status postvasectomy), who:
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
In the absence of rapid progressive disease, the interval from prior systemic anticancer treatment to time of TAK-659 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea), or at least 5 half-lives for noncytotoxic agents, and participants have to have recovered from acute toxicities of these therapies. Participants who are on hydroxyurea may be included in the study and may continue on hydroxyurea for the first 28 days while participating in this study.
Suitable venous access for the study-required blood sampling, including pharmacokinteic (PK) and pharmacodynamic (PD) sampling and blood transfusion support.
Clinical laboratory values as specified in the following:
Exclusion criteria
Clinically active central nervous system leukemia.
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
Any serious medical or psychiatric illness, including drug or alcohol abuse that could, in the investigator's opinion, potentially jeopardize the safety of the participant or interfere with the objectives of the study.
Systemic anti-cancer treatment (including investigational agents) <=21 days or <= 5*their half-lives before the first dose of study treatment. (For example, if the 5*the half-life is shorter than 21 days, 5*half-life should be used as the washout period. However, a minimum of 10 days should elapse from prior therapy to initiating protocol therapy).
Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).
Receipt of hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of TAK-659; clinically significant graft-versus-host disease (GVHD) requiring ongoing immunosuppressive therapy post HSCT at the time of screening (use of topical steroids for ongoing skin GVHD is permitted).
Active, systemic infection requiring intravenous (IV) antibiotic, antifungal, or antiviral therapy or other serious infection within 14 days before the first dose of study drug.
Major surgery within 14 days before the first dose of study drug and have not recovered fully from any complications from surgery.
Radiotherapy less than 2 weeks before the first dose of study treatment or have not recovered from acute toxic effects from radiotherapy.
Known human immunodeficiency virus (HIV) positive (testing not required).
Known hepatitis B surface antigen-positive, known or suspected active hepatitis C infection (testing not required).
Evidence of currently uncontrolled cardiovascular conditions as listed in the protocol; acute myocardial infarction with 6 months before starting study drug; baseline QT interval (QTcF) greater than (>) 450 milliseconds (msec) (males) or > 475 msec (females); or abnormalities on baseline 12-lead electrocardiogram (ECG) that are considered clinically significant per investigator.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659 including difficulty swallowing tablets; diarrhea > Grade 1 despite supportive therapy.
Use or consumption of any of the following substances:
White blood cell count > 50,000 per micro liter (/µL); hydroxyurea may be used to control the level of circulating leukemic blast cell counts prior to study entry and, if needed, concomitantly while on TAK-659 treatment during the first 28 days of the study. Hydroxyurea can be used up to a maximum dose of 5 gram per (g/) day.
Primary purpose
Allocation
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Masking
43 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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