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Trial record 1 of 1 for:    C34002
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Safety, Tolerability, and Efficacy of TAK-659 in Adults With Relapsed or Refractory Acute Myelogenous Leukemia (AML)

This study is currently recruiting participants.
Verified June 2017 by Takeda ( Millennium Pharmaceuticals, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02323113
First Posted: December 23, 2014
Last Update Posted: June 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
  Purpose
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 patients 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).

Condition Intervention Phase
Acute Myelogenous Leukemia Drug: TAK-659 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1b/2 Study Investigating Recommended Phase 2 Dose, Safety, Tolerability, and Preliminary Efficacy of TAK-659 in Adult Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Takeda ( Millennium Pharmaceuticals, Inc. ):

Primary Outcome Measures:
  • Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 28 days after last dose of study drug ]

    An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. AEs will be recorded from first dose of study drug through 28 days after the last dose of study drug or to the start of anticancer therapy, whichever occurs first.

    A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. SAEs will be reported from signing of informed consent form through 28 days after the last dose of study drug even if the patient starts nonprotocol therapy.


  • Phase 1b: Cycle 1 Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Days 1 through 42) ]
    DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with TAK-659.

  • Phase 1b: Number of Participants With Clinically Significant Laboratory Findings [ Time Frame: From Day 1 through 28 days after the last dose of study drug (up to 13 months) ]
    The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study.

  • Phase 1b: Number of Participants With Clinically Significant Vital Sign Findings [ Time Frame: From Day 1 through 28 days after the last dose of study drug (up to 13 months) ]
    The number of participants with any markedly abnormal vital sign values will be collected throughout study.

  • Phase 2: Overall Response Rate (ORR) [ Time Frame: Days 22 to 28 of Cycles 1, 2, and 4, Cycle 5 and beyond as needed ]
    ORR is defined as the percentage of participants with complete response (CR), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (Cri), and partial response (PR).


Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: From first documented response until disease progression (Up to 13 months) ]
    Duration of response is defined as the time from the date of first documentation of a response to the date of first documentation of disease progression.

  • Time to Progression (TTP) [ Time Frame: From the date randomization to the date of first documented progressive disease (Up to 13 months) ]
    TTP is defined as the time from baseline to the date of first documentation of progressive disease.

  • Mortality Rate [ Time Frame: Months 3 and 6 ]
    Rate of death at 3 and 6 months.

  • Overall Survival (OS) [ Time Frame: Cycle 1 Day 1 through 12 months after discontinuation of study drug ]
    Overall survival is defined as the time from study entry to the time of death.

  • Overall Response Rate (ORR) in FLT-3-ITD Mutant Versus Wild Type (WT) Populations [ Time Frame: Days 22 to 28 of Cycles 1, 2, and 4, Cycle 5 and beyond as needed ]
    ORR is defined as the percentage of participants with complete response (CR), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (Cri), and partial response (PR).

  • Duration of Response (DOR) in FLT-3-ITD Mutant Versus Wild Type (WT) Populations [ Time Frame: From first documented response until disease progression (Up to 13 months) ]
    Duration of response is defined as the time from the date of first documentation of a response to the date of first documentation of disease progression.

  • Time to Progression (TTP) in FLT-3-ITD Mutant Versus Wild Type (WT) Populations [ Time Frame: From the date randomization to the date of first documented progressive disease (Up to 13 months) ]
    TTP is defined as the time from baseline to the date of the first documentation of progressive disease.

  • Mortality Rate in FLT-3-ITD Mutant Versus Wild Type (WT) Populations [ Time Frame: Months 3 and 6 ]
    Rate of death at 3 and 6 months.

  • Overall Survival (OS) in FLT-3-ITD Mutant Versus Wild Type (WT) Populations [ Time Frame: Cycle 1 Day 1 through 12 months after discontinuation of study drug ]
    Overall survival is defined as the time from the date of first study entry to death.

  • Cmax: Maximum Observed Plasma Concentration for TAK-659 [ Time Frame: Cycle 1, Day 1 and Day 15 ]
    Maximum observed plasma concentration (Cmax) is the observed peak plasma concentration of a drug after administration.

  • Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-659 [ Time Frame: Cycle 1, Day 1 and 15 ]
    Time to reach the maximum observed plasma concentration (Cmax) of a drug after administration.

  • AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-659 [ Time Frame: Cycle 1, Day 1 and 15 ]
    Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.

  • Apparent Clearance (CL/F) for TAK--659 [ Time Frame: Cycle 1, Day 1 and 15 ]
    Apparent clearance after extravascular administration, calculated as Dose/AUC∞ after a single dose and as Dose/AUCtau after multiple dosing (at steady state).

  • Accumulation Ratio (Rac) for TAK-659 [ Time Frame: Cycle 1 Day 15 ]
    Accumulation ratio (based on AUC), calculated as AUCtau after multiple dosing (at steady state)/AUCtau after a single dose.

  • Peak Trough Ratio (PTR) for TAK-659 [ Time Frame: Cycle 1 Day 15 ]
    The ratio of the maximum observed plasma concentration to the observed trough plasma concentration, where trough concentration is the concentration at the end of the dosing interval at steady-state before the next dose is administered.

  • Pharmacodynamic (PD) Effect Measured as Modulation of Expression of Pathway Markers in Peripheral Acute Myelogenous Leukemia AML Blasts [ Time Frame: Screening and Cycle 1 Days 1 and 15 pre-dose and at multiple timepoints post-dose ]

Estimated Enrollment: 81
Actual Study Start Date: February 19, 2015
Estimated Study Completion Date: November 16, 2020
Estimated Primary Completion Date: May 16, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b: TAK-659
TAK-659 tablets taken orally, once daily on Days 1-28 in a 28 day cycle, for up to 12 cycles or until disease progression. Dosage of TAK-659 may increase in 20 mg increments using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).
Drug: TAK-659
TAK-659 tablets taken orally once daily.
Experimental: Phase 2:
TAK-659, tablets taken orally, once daily on Days 1-28 in a 28 day cycle, for up to 12 cycles or until disease progression. Dosage for this phase will be determined from results of Phase 1b MTD/RP2D.
Drug: TAK-659
TAK-659 tablets taken orally once daily.

Detailed Description:

The drug being tested in this study is called 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 81 patients (up to 15 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 patients with FLT-3 ITD mutations and the other for FLT-3 wild-type patients.

Phase 1b:

• TAK-659 60 mg tablet starting dose escalated in 20 mg or higher increments to a maximum tolerated dose or recommended Phase 2 dose (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-centre trial will be conducted in the United States and Canada. 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants 18 years or older.
  2. Must have a histopathologically documented diagnosis of primary or secondary acute myelogenous leukemia (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).
  3. Participants for the phase 2 portion of the study must, in addition, meet the following:

    1. 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.
    2. Must not have prior exposure to any investigational FLT-3 inhibitors.
  4. Eastern Cooperative Oncology Group performance status of 0 to 1.
  5. a.Female participants who:

    • Are postmenopausal for at least 1 year before the screening visit, or
    • Are surgically sterile, or
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.

    (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.) b. Male participants, even if surgically sterilized (ie, status postvasectomy), who:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.

    (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)

  6. 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.
  7. 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.
  8. Suitable venous access for the study-required blood sampling, including PK and PD sampling and blood transfusion support.
  9. Participants must have adequate organ function as specified in the following:

    • Total bilirubin must be ≤ 1.5 x the upper limit of normal (ULN).
    • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 2.5 x the ULN.
    • Serum creatinine must be < 1.5 x ULN or creatinine clearance ≥ 50 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours).

Exclusion Criteria:

  1. Clinically active central nervous system leukemia.
  2. 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.
  3. 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.
  4. Prior treatment with investigational agents ≤ 21 days or ≤ 5 x their half-lives (whichever is shorter) before the first dose of study treatment. A minimum of 10 days should elapse from prior investigational therapy to initiating protocol therapy.
  5. 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).
  6. 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).
  7. 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.
  8. Major surgery within 14 days before the first dose of study drug and have not recovered fully from any complications from surgery.
  9. Radiotherapy less than 2 weeks before the first dose of study treatment or have not recovered from acute toxic effects from radiotherapy.
  10. Known human immunodeficiency virus (HIV) positive (testing not required).
  11. Known hepatitis B surface antigen-positive, known or suspected active hepatitis C infection (testing not required).
  12. 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) > 450 milliseconds (msec) (males) or > 475 msec (females); or abnormalities on baseline 12-lead ECG that are considered clinically significant per investigator.
  13. 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.
  14. Use or consumption of any of the following medications, supplements, or foods/beverages that are inhibitors or inducers of P-gp or strong inhibitors or inducers of CYP3A within the indicated timeframes below. Note that use or consumption of these substances is not permitted during the study.

    1. Inhibitors of P-gp and/or strong reversible inhibitors of CYP3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known), or within 7 days (if a reasonable half-life estimate is unknown), before the first dose of study drug. See Section 14.5 for a list of prohibited strong CYP3A reversible inhibitors and/or P-gp inhibitors based on the FDA Draft DDI Guidance.
    2. Strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers within 7 days, or within 5 times the inhibitor or inducer half-life (whichever is longer), before the first dose of study drug. See Section 14.5 for a list of prohibited strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers based on the FDA Draft DDI Guidance.
    3. Grapefruit-containing food or beverages within 5 days before the first dose of study drug.
  15. White blood cell count > 50,000/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 g/day.
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02323113


Contacts
Contact: Takeda Study Registration Call Center +1-844-662-8532 globaloncologymedinfo@takeda.com

Locations
United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35233
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center of Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Oncology Specialists, S.C. Not yet recruiting
Niles, Illinois, United States, 60714
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Center Not yet recruiting
Detroit, Michigan, United States, 48201
Henry Ford Health System Not yet recruiting
Detroit, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
United States, New York
North Shore Long Island Jewish Medical Center Not yet recruiting
New York, New York, United States, 10024
United States, North Carolina
University of North Carolina Hospital Not yet recruiting
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
UC Health Clinical Trials Office Recruiting
Cincinnati, Ohio, United States, 45206
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75204
United States, Wisconsin
Medical College of Wisconsin, Inc. Not yet recruiting
Milwaukee, Wisconsin, United States, 53266
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre Not yet recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Princess Margaret Hospital Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Wake Forest University Baptist Medical Center Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02323113     History of Changes
Other Study ID Numbers: C34002
U1111-1163-2185 ( Registry Identifier: WHO )
First Submitted: December 18, 2014
First Posted: December 23, 2014
Last Update Posted: June 9, 2017
Last Verified: June 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug therapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms