Clinical Trials /

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

NCT03238651

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of TAK-659 as a Single Agent in Adult East Asian Participants With Non-Hodgkin Lymphoma (NHL)
  • Official Title: A Phase 1, Open-label Study of TAK-659 as a Single Agent in Adult East Asian Patients With Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: C34007
  • SECONDARY ID: U1111-1186-6838
  • NCT ID: NCT03238651

Conditions

  • Lymphoma, Non-Hodgkin
  • Lymphoma, Follicular, Marginal Zone

Interventions

DrugSynonymsArms
TAK-659Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1ExperimentalTAK-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.
  • TAK-659
Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1ExperimentalTAK-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.
  • TAK-659
Expansion Part: TAK-659 MTD/RP2DExperimentalTAK-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.
  • TAK-659

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame:Up to 52 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Expansion Part: Overall Response Rate (ORR)
Time Frame:Up to 52 months
Safety Issue:
Description: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.
Measure:Expansion Part: CR Rate
Time Frame:Up to 52 months
Safety Issue:
Description: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.
Measure:Expansion Part: Duration of Response (DOR)
Time Frame:Up to 52 months
Safety Issue:
Description: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.
Measure:Expansion Part: Progression-free Survival (PFS)
Time Frame:Up to 52 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug therapy

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