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Trial record 1 of 1 for:    C34004
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TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03123393
Recruitment Status : Terminated (Lack of efficacy of the drug; no safety concern)
First Posted : April 21, 2017
Last Update Posted : April 10, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: TAK-659 Phase 2

Detailed Description:

The drug being tested is TAK-659. This study will look at the OR in participants with relapsed or refractory DLBCL who take TAK-659.

The study will enroll approximately 122 participants. Participants will be assigned to:

• TAK-659 60 mg to 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, Canada, Germany. The overall time to participate in this study is approximately 48 months. Participants will be assessed for disease response and progression during the PFS follow-up of every 3 months after end of treatment (for participants who discontinue due to reasons other than disease progression) and OS follow-up of every 3 months from the last dose of study drug until death or conclusion of the study, whichever occurs first.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 10, 2017
Actual Primary Completion Date : January 7, 2020
Actual Study Completion Date : January 7, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: TAK-659
TAK-659, 60 milligram (mg) to 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).
Drug: TAK-659
TAK-659 Tablets




Primary Outcome Measures :
  1. ORR as Assessed by IRC Based on Modified 2007 International Working Group (IWG) Criteria (Stage 2) [ Time Frame: Up to 12 months ]
    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 :
  1. CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria (Stage 2) [ Time Frame: Up to 12 months ]
    CR rate is defined as percentage of participants with complete response as assessed by IRC according to the modified 2007 IWG.

  2. ORR as Assessed by IRC Based on 2014 IWG-Lugano Criteria (Stage 2) [ Time Frame: Up to 12 months ]
    ORR is defined as the percentage of participants with CR or PR as assessed by IRC according to the 2014 Lugano classification, IWG criteria.

  3. CR Rate as Assessed by IRC Based on 2014 IWG-Lugano Criteria (Stage 2) [ Time Frame: Up to 12 months ]
    CR rate is defined as percentage of participants with complete response as assessed by IRC according to the 2014 Lugano classification, IWG criteria.

  4. Duration of Response (DOR) (Stage 2) [ Time Frame: Up to 12 months ]
    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.

  5. Duration of CR (Stage 2) [ Time Frame: Up to 12 months ]
    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.

  6. ORR as Assessed by IRC in Participants with Germinal Center B-cell (GCB) DLBCL (Stage 2) [ Time Frame: Up to 12 months ]
    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.

  7. ORR as Assessed by IRC in Participants with DLBCL Transformed from Indolent non-Hodgkin Lymphoma (NHL) (Stage 2) [ Time Frame: Up to 12 months ]
    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.

  8. Progression Free Survival (PFS) as Assessed by IRC (Stage 2) [ Time Frame: Up to 18 months ]
    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.

  9. Overall Survival (OS) (Stage 2) [ Time Frame: Up to 24 months ]
    OS is defined as the time from start of study treatment to date of death due to any cause.

  10. ORR as Assessed by IRC to Select the Dose Regimen of TAK-659 from the Lead-in Dose Exploration Phase (Stage 2) [ Time Frame: Up to 12 months ]
    ORR is defined as the percentage of participants with CR or PR as assessed by IRC.

  11. ORR as Assessed by IRC at 3, 6, and 9 cycles in Participants with DLBCL (Stage 2) [ Time Frame: Up to 12 months ]
    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.



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Must have histologically confirmed DLBCL, including de novo disease or transformed disease from indolent NHL.

    a. High-grade B-cell lymphoma (BCL) with MYC and BCL-2 and/or BCL-6 translocations (double-hit DLBCL under DLBCL, not otherwise specified [NOS], based on the 2008 World Health Organization [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.
  3. Relapsed or refractory to greater than or equal to (>=) 2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
  4. Documented investigator-assessed relapse or progression after the last treatment is required if the participant responded and then progressed on the prior treatment.
  5. Measurable disease per IWG 2007 criteria.
  6. Eastern Cooperative Oncology Group (ECOG) performance status less than (<) 2.
  7. Life expectancy of greater than (>) 3 months.
  8. Adequate organ function, including the following:

    1. Bone marrow reserve: absolute neutrophil count (ANC) >=1000/microliter (μL), platelet count >=75,000/μL (>=50,000/μL for participants with bone marrow involvement), and hemoglobin >=8 gram per deciliter (g/dL).
    2. Hepatic: total bilirubin less than or equal to (<=) 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 milliliter per minute (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.
      • Glycosylated hemoglobin is <=6.5% hyperglycemic participants permitted if glucose is well controlled by hypoglycemic medication).

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 fluorodeoxyglucose-positron emission tomography (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 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 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.

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): NCT03123393


Locations
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Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.
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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03123393    
Other Study ID Numbers: C34004
U1111-1187-6208 ( Other Identifier: WHO )
2016-003716-12 ( EudraCT Number )
17/YH/0181 ( Registry Identifier: NRES )
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: April 10, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
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.

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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:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin