Clinical Trials /

TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

NCT03123393

Description:

The purpose of this study is to assess the efficacy of TAK-659 measured by independent radiologic review committee (IRC)-assessed overall response rate (ORR) in participants with relapsed or refractory DLBCL.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
  • Official Title: Phase 2 Study of TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After at Least 2 Prior Lines of Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: C34004
  • SECONDARY ID: U1111-1187-6208
  • SECONDARY ID: 2016-003716-12
  • NCT ID: NCT03123393

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
TAK-659TAK-659

Purpose

The purpose of this study is to assess the efficacy of TAK-659 measured by independent radiologic review committee (IRC)-assessed overall response rate (ORR) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Detailed Description

      The drug being tested is TAK-659. This study will look at the overall response in
      participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who take
      TAK-659.

      The study will enroll approximately 82 patents. Participants will be assigned to:

      • TAK-659 100 mg

      All participants will be asked to take the tablets of TAK-659 at the same time each day
      throughout the study in 28-day cycle.

      This multi-center trial will be conducted in United States, United Kingdom, Spain, Italy,
      France. The overall time to participate in this study is approximately 35 months.
      Participants will be assessed for disease response and progression during the progression
      free survival (PFS) follow-up of every 3 months after end of treatment (for participants who
      discontinue due to reasons other than disease progression) and overall survival follow-up of
      every 3 months from the last dose of study drug until death or conclusion of the study,
      whichever occurs first.
    

Trial Arms

NameTypeDescriptionInterventions
TAK-659ExperimentalTAK-659, 100 mg, tablets, orally, once daily in 28-day cycle until disease progression, unacceptable toxicities, or withdrawal for other reasons (estimated median treatment duration 6 months).
  • TAK-659

Eligibility Criteria

        Inclusion Criteria:

          1. Must have histologically confirmed diffuse large B-cell lymphoma (DLBCL), including de
             novo disease or transformed disease from indolent non-Hodgkin lymphoma (NHL).

             a. High-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 translocations
             (double-hit DLBCL under DLBCL, NOS, based on the 2008 WHO classification criteria) is
             not eligible for this study.

          2. Local pathology review for histological confirmation; A formalin-fixed,
             paraffin-embedded (FFPE) tumor block or appropriately stained slides from a fresh
             biopsy is required.

             Relapsed or refractory to ≥2 prior lines of chemotherapy based on standard of care
             with certain requirements for prior therapy.

          3. Documented investigator-assessed relapse or progression after the last treatment is
             required if the participant responded and then progressed on the prior treatment.

          4. Measurable disease per IWG 2007 criteria.

          5. Eastern Cooperative Oncology Group (ECOG) performance status <2.

          6. Life expectancy of >3 months.

          7. Adequate organ function, including the following:

               1. Bone marrow reserve: absolute neutrophil count (ANC) ≥1000/μL, platelet count
                  ≥75,000/μL (≥50,000/μL for participants with bone marrow involvement), and
                  hemoglobin ≥8 g/dL.

               2. Hepatic: total bilirubin ≤1.5 times the upper limit of the normal range (ULN);
                  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5*ULN.

               3. Renal: creatinine clearance ≥60 mL/min.

               4. Others:

                    -  Lipase ≤1.5*ULN and amylase ≤1.5*ULN with no clinical symptoms suggestive of
                       pancreatitis or cholecystitis.

                    -  Blood pressure ≤Grade 1 (hypertensive participants are permitted if their
                       blood pressure is controlled to ≤Grade 1 by hypertensive medications and
                       glycosylated hemoglobin is ≤6.5%).

        Exclusion Criteria:

          1. Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases.

          2. Known human immunodeficiency virus (HIV)-related malignancy.

          3. 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 agents; ≤8 weeks for cell-based therapy or anti-tumor vaccine).

          4. Radiotherapy less than 3 weeks before the first dose of study treatment. If prior
             radiotherapy occurred <4 to 6 weeks before study start, as radiated lesions cannot be
             reliably assessed by FDG-PET, nonradiated target lesions are required for eligibility,
             and prior radiotherapy information must be submitted to the IRC.

          5. Known HIV positive, hepatitis B surface antigen positive or known or suspected active
             hepatitis C infection.

          6. Prior ASCT within 6 months or prior ASCT at any time without full hematopoietic
             recovery before Cycle 1 Day 1, or allogeneic stem cell transplant any time.

          7. Participants with certain cardiovascular conditions are excluded.

          8. Major surgery within 14 days before the first dose of study drug or incomplete
             recovery from any complications from surgery.

          9. Systemic infection requiring parenteral antibiotic therapy or other serious infection
             (bacterial, fungal, or viral) within 21 days before the first dose of study drug.

         10. Treatment with high-dose corticosteroids for anticancer purposes within 7 days before
             the first dose of TAK-659.

         11. Participants with another malignancy within 2 years of study start. Participants with
             nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have
             undergone complete resection and are considered disease-free at the time of study
             entry.

         12. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of TAK-659.

         13. 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 timeframe 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:Overall Response Rate (ORR) as Assessed by Independent Radiologic Review Committee (IRC) Based on Modified 2007 International Working Group (IWG) Criteria
Time Frame:Up to 12 months
Safety Issue:
Description:ORR is defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma.

Secondary Outcome Measures

Measure:Complete Response (CR) Rate as Assessed by IRC Based on Modified 2007 IWG Criteria
Time Frame:Up to 12 months
Safety Issue:
Description:CR rate is defined as percentage of participants with complete response as assessed by IRC according to the modified 2007 IWG.
Measure:Overall Response Rate (ORR) as Assessed by IRC Based on 2014 IWG-Lugano Criteria
Time Frame:Up to 12 months
Safety Issue:
Description:ORR is defined as the percentage of participants with CR or PR as assessed by IRC according to the 2014 Lugano classification, IWG criteria.
Measure:Complete Response (CR) Rate as Assessed by IRC Based on 2014 IWG-Lugano Criteria
Time Frame:Up to 12 months
Safety Issue:
Description:CR rate is defined as percentage of participants with complete response as assessed by IRC according to the 2014 Lugano classification, IWG criteria.
Measure:Durable Response Rate (DRR),
Time Frame:Up to 12 months
Safety Issue:
Description:DRR is defined as percentage of participants who have durable responses. Durable response is defined as a CR/PR with duration ≥16 weeks, which is equivalent to 4 cycles for 28-day cycles as per IRC.
Measure:Duration of Response (DOR)
Time Frame:Up to 12 months
Safety Issue:
Description:DOR is defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or progressive disease (PD) per IRC assessment according to IWG criteria.
Measure:Duration of Complete Response
Time Frame:Up to 12 months
Safety Issue:
Description:Duration of CR is defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or PD per IRC assessment according to IWG criteria.
Measure:Overall Response Rate (ORR) as Assessed by IRC in Participants with Germinal Center B-cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL)
Time Frame:Up to 12 months
Safety Issue:
Description:ORR is defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma.
Measure:Overall Response Rate (ORR) as Assessed by IRC in Participants with DLBCL Transformed from Indolent non-Hodgkin Lymphoma (NHL)
Time Frame:Up to 12 months
Safety Issue:
Description:ORR is defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma.
Measure:Progression Free Survival (PFS) as Assessed by IRC
Time Frame:Up to 18 months
Safety Issue:
Description:PFS is defined as time from start of study treatment to first documentation of PD per IRC assessment or up to death due to any cause, whichever occurs first based on IWG criteria.
Measure:Overall Survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:OS is defined as the time from start of study treatment to date of death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug therapy

Last Updated

December 1, 2017