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A Study of TAK-659 as a Single Agent in Adult East Asian Participants With Non-Hodgkin Lymphoma (NHL)

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ClinicalTrials.gov Identifier: NCT03238651
Recruitment Status : Recruiting
First Posted : August 3, 2017
Last Update Posted : February 11, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE August 1, 2017
First Posted Date  ICMJE August 3, 2017
Last Update Posted Date February 11, 2019
Actual Study Start Date  ICMJE August 1, 2017
Estimated Primary Completion Date March 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 52 months ]
  • Percentage of Participants With Grade 3 or Higher TEAEs [ Time Frame: Up to 52 months ]
  • Percentage of Participants With Serious TEAEs [ Time Frame: Up to 52 months ]
  • Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 [ Time Frame: Up to dosing on Cycle 2 Day 1 ]
  • Percentage of Participants Discontinuing Study Drug Because of TEAEs [ Time Frame: Up to 52 months ]
  • Percentage of Participants With Clinically Significant Laboratory Values [ Time Frame: Up to 52 months ]
  • Percentage of Participants With Clinically Significant Vital Sign Measurements [ Time Frame: Up to 52 months ]
  • Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) ]
  • Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 or 15 [ Time Frame: Schedule A Day 15 and Schedule B Day 7: pre-dose and at multiple time points (up to 24 hours) ]
  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) ]
  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 or 15 [ Time Frame: Schedule A Day 15 and Schedule B Day 7: pre-dose and at multiple time points (up to 24 hours) ]
  • AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659 on Cycle 1 Day 1 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) ]
  • AUCτ: Area Under the Plasma Concentration-time Curve from Time During the Dosing Interval for TAK-659 on Cycle 1 Day 7 or 15 [ Time Frame: Schedule A Day 15 and Schedule B Day 7: pre-dose and at multiple time points (up to 24 hours) ]
  • Renal Clearance (CLR) for TAK-659 on Cycle 1 Day 7 or 15 [ Time Frame: Schedule A Day 15 and Schedule B Day 7: pre-dose and at multiple time points (up to 24 hours) ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2017)
  • Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 6 months ]
  • Percentage of Participants With Grade 3 or Higher TEAEs [ Time Frame: Up to 6 months ]
  • Percentage of Participants With Serious TEAEs [ Time Frame: Up to 6 months ]
  • Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 [ Time Frame: Up to dosing on Cycle 2 Day 1 ]
  • Percentage of Participants Discontinuing Study Drug Because of TEAEs [ Time Frame: Up to 6 months ]
  • Percentage of Participants With Clinically Significant Laboratory Values [ Time Frame: Up to 6 months ]
  • Percentage of Participants With Clinically Significant Vital Sign Measurements [ Time Frame: Up to 6 months ]
  • Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1 [ Time Frame: Day 15 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [diffuse large B-cell lymphoma (DLBCL expansion part)] post-dose ]
  • Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 15 [ Time Frame: Day 15 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [DLBCL expansion part]) post-dose ]
  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [DLBCL expansion part]) post-dose ]
  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 15 [ Time Frame: Day 15 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [DLBCL expansion part]) post-dose ]
  • AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659 on Cycle 1 Day 1 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [DLBCL expansion part]) post-dose ]
  • AUCτ: Area Under the Plasma Concentration-time Curve from Time During the Dosing Interval for TAK-659 on Cycle 1 Day 15 [ Time Frame: Day 15 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [DLBCL expansion part]) post-dose ]
  • Renal Clearance (CLR) for TAK-659 on Cycle 1 Day 15 [ Time Frame: Day 15 pre-dose and at multiple time points (up to 8 hours [dose escalation part] and up to 4 hours [DLBCL expansion part]) post-dose ]
Change History Complete list of historical versions of study NCT03238651 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Expansion Part: Overall Response Rate (ORR) [ Time Frame: Up to 52 months ]
    The percentage of participants in the response-evaluable population of the expansion part who achieved either complete remission (CR) or partial remission (PR), as assessed by investigators, according to modified International Working Group (IWG) criteria for malignant lymphoma. CR is defined as disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
  • Expansion Part: CR Rate [ Time Frame: Up to 52 months ]
    The percentage of participants in the response-evaluable population of the expansion part who achieved CR, as assessed by investigator, according to modified IWG criteria for malignant lymphoma. CR is defined as disappearance of all evidence of disease.
  • Expansion Part: Duration of Response (DOR) [ Time Frame: Up to 52 months ]
    The time from first documentation of response (CR/PR) to the date of first documentation of PD/relapse, as assessed by investigator, according to modified IWG criteria for malignant lymphoma in the response-evaluable population of the expansion part. CR is defined as disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. Progressive disease (PD) is defined as any new lesion or increase by greater than or equal to (>=) 50 percent (%) of previously involved sites from nadir.
  • Expansion Part: Progression-free Survival (PFS) [ Time Frame: Up to 52 months ]
    The time from the date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurs first, in the safety population of the expansion part, as assessed by the investigator, according to modified IWG criteria for malignant lymphoma. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2017)
  • DLBCL Expansion Part: Overall Response Rate (ORR) [ Time Frame: Up to 6 months ]
    The percentage of participants in the response-evaluable population of the DLBCL expansion part who achieved either complete remission (CR) or partial remission (PR), as assessed by investigators, according to modified International Working Group (IWG) criteria for malignant lymphoma. CR is defined as disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
  • DLBCL Expansion Part: Duration of Response (DOR) [ Time Frame: Up to 6 months ]
    The time from first documentation of response (CR/PR) to the date of first documentation of PD/relapse, as assessed by investigator, according to modified IWG criteria for malignant lymphoma in the response-evaluable population of the DLBCL expansion part. CR is defined as disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. Progressive disease (PD) is defined as any new lesion or increase by greater than or equal to (>=) 50 percent (%) of previously involved sites from nadir.
  • DLBCL Expansion Part: Time to Progression (TTP) [ Time Frame: Up to 6 months ]
    The time from the date of first study drug administration to the day of first documented PD, as assessed by investigator, according to modified IWG criteria for malignant lymphoma in the safety population of the DLBCL expansion part. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir.
  • DLBCL Expansion Part: Progression-free Survival [ Time Frame: Up to 6 months ]
    The time from the date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurs first, in the safety population of the DLBCL expansion part, as assessed by the investigator, according to modified IWG criteria for malignant lymphoma. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir.
  • DLBCL Expansion Part: CR Rate [ Time Frame: Up to 6 months ]
    The percentage of participants in the response-evaluable population of the DLBCL expansion part who achieved CR, as assessed by investigator, according to modified IWG criteria for malignant lymphoma. CR is defined as disappearance of all evidence of disease.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of TAK-659 as a Single Agent in Adult East Asian Participants With Non-Hodgkin Lymphoma (NHL)
Official Title  ICMJE A Phase 1, Open-label Study of TAK-659 as a Single Agent in Adult East Asian Patients With Non-Hodgkin Lymphoma
Brief Summary The purpose of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 when administered in East Asian participants with NHL who do not have an effective standard treatment available and to characterize the plasma and urine pharmacokinetic (PK) of TAK-659 in East Asian participants with NHL.
Detailed Description

The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat people who have NHL or people who have relapsed and/or refractory NHL. This study will assess the safety, tolerability, PK, and preliminary efficacy of single-agent TAK-659 in East Asian participants with NHL.

The study will enroll approximately 33 to 47 participants, including at least 6 Japanese at RP2D dose level. Participants will be assigned to one of the following treatment groups:

Dose Escalation Part: TAK-659 Expansion Part: TAK-659 RP2D

This multi-center trial will be conducted in Japan and Republic of Korea. The maximum duration of participation in dose escalation part of the study is up to 12 months, unless in the opinion of the investigator and sponsor the participant would derive benefit from continued therapy beyond 12 months. In expansion part, participants who stop treatment for any other reason other than PD will continue to have PFS follow-up at the site every 2 months from the last dose of study drug up to 6 months or until PD. Participants will be followed 28 days after last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurs first, for a follow up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Follicular, Marginal Zone
Intervention  ICMJE Drug: TAK-659
TAK-659 Tablets.
Study Arms  ICMJE
  • Experimental: Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1
    TAK-659, tablet, orally, once daily, in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 60 milligram (mg) in Cohort 1. Dose escalation will follow a standard 3+3 schema . If 60 mg, once daily is safe and tolerable, then the dose will be escalated to 80 mg, once daily and subsequently in 20 mg increments until MTD and/or RP2D is determined. Based on emerging safety, tolerability, PK data, a lower dose will be permitted.
    Intervention: Drug: TAK-659
  • Experimental: Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1
    TAK-659, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 80 mg in Cohort 1. Dose escalation will follow a standard 3+3 schema. An alternative intermittent regimen may be evaluated if deemed necessary per the emerging data.
    Intervention: Drug: TAK-659
  • Experimental: Expansion Part: TAK-659 MTD/RP2D
    TAK-659, tablet, orally, once daily, in a 28-day treatment cycle until disease progression or unacceptable toxicity in participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL) who are relapsed and/or refractory. Dose and dosing schedule for this part will be MTD/RP2D determined from results of dose escalation part.
    Intervention: Drug: TAK-659
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2019)
47
Original Estimated Enrollment  ICMJE
 (submitted: August 1, 2017)
38
Estimated Study Completion Date  ICMJE August 28, 2020
Estimated Primary Completion Date March 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. To be enrolled to the dose escalation part, participants must have histologically or cytologically confirmed diagnosis of NHL for which no effective standard treatment is available.
  2. To be enrolled in the expansion part, participants must meet the following criteria:

    1. Must have pathologically confirmed FL (Grade 1, 2, or 3A) or MZL.
    2. Relapsed and/or refractory to >=2 prior lines of chemotherapy based on standard of care that include at least 1 anti-CD20-based regimen, as well as alkylating agents (example cyclophosphamide or bendamustine).
    3. Participants must be ineligible for or refusal to hematopoietic stem cell transplant.
    4. If the participants have relapsed or progressed after achieving a response (defined as CR or PR), documented, investigator-assessed relapse or progression after the last treatment is required.
  3. Measurable disease per IWG 2007 criteria.
  4. Eastern Cooperative Oncology Group performance status score of 0 or 1.
  5. Life expectancy of longer than 3 months.
  6. Adequate organ function, including the following:

    1. Bone marrow reserve: absolute neutrophil count >=1,000 per cubic millimeter (/mm^3), platelet count >=75,000/mm^3 (>=50,000/mm^3 for participants with bone marrow involvement), and hemoglobin >=8 gram per deciliter (g/dL) (red blood cell [RBC] and platelet transfusion allowed >=14 days before assessment).
    2. Hepatic function: total bilirubin less than or equal to (<=) 1.5*the upper limit of the normal range (ULN); alanine aminotransferase and aspartate aminotransferase <=2.5*ULN.
    3. Renal function: creatinine clearance >=60 milliliter per minute (mL/min) either as estimated by the Cockcroft-Gault equation.

Exclusion Criteria:

  1. Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases as indicated by positive cytology from lumbar puncture or computed tomography (CT)/magnetic resonance imaging (MRI) by local assessment.
  2. Systemic anticancer treatment (including investigational agents) less than 3 weeks before the first dose of study treatment (<=4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agent; <=8 weeks for cell-based therapy or anti-tumor vaccine).
  3. Radiotherapy less than (<) 3 weeks before the first dose of study treatment. If prior radiotherapy occurred <4 to 6 weeks before the study start, as radiated lesions cannot be reliably assessed by fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET), nonradiated target lesions are required for eligibility.
  4. Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time without full hematopoietic recovery before Cycle 1 Day 1, or allogeneic stem cell transplant at any time.
  5. Any clinically significant comorbidities, such as uncontrolled pulmonary disease (example, severe chronic obstructive pulmonary disease with hypoxemia, interstitial lung disease, radiation induced lung injury), known impaired cardiac function or clinically significant cardiac disease, active CNS disease, or any other condition that could, in the opinion of the investigator, compromise the participant's safety and participation in the study per protocol.
  6. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659.
  7. Use or consumption of any of the following substances:

Received medications, supplements, or food/beverages that are P-glycoprotein (P-gp) inhibitors or inducers or strong cytochrome P450 (CYP) 3A inhibitors or inducers within a certain time frame prior to the first dose of study drug. Depending on the substance, the washout period for P-gp inhibitors or inducers or strong CYP3A inhibitors or inducers will be either 7 days or 5 times the half-life (half-life is related to the time required for elimination from the body). The washout period for grapefruit containing food or beverages is 5 days.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com
Listed Location Countries  ICMJE Japan,   Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03238651
Other Study ID Numbers  ICMJE C34007
U1111-1186-6838 ( Registry Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.
PRS Account Takeda
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP