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

NCT03123393 | Terminated Phase 2 Results FDA Drug

• 4 other identifiers: C34004U1111-1187-62082016-003716-1217/YH/0181
• Study Type: interventional
• Target: 49
• Locations: 6 countries
• Sites: 41

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.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria

  ORR was defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

  Up to 12 months

Secondary Outcomes (11)

• Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria

  Up to 12 months

• Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria

  Up to 12 months

• Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria

  Up to 12 months

• Stage 2: Duration of Response (DOR)

  Up to 12 months

• Stage 2: Duration of CR

  Up to 12 months

Study Arms (2)

Cohort A: TAK-659 100 mg

EXPERIMENTAL

TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).

Drug: TAK-659

Cohort B: TAK-659 Ramp-up Dosing

EXPERIMENTAL

TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).

Drug: TAK-659

Interventions

TAK-659 DRUG

TAK-659 Tablets

Cohort A: TAK-659 100 mg; Cohort B: TAK-659 Ramp-up Dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 greater than or equal to (\>=) 2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
• Documented investigator-assessed relapse or progression after the last treatment is required if the participant responded and then progressed on the prior treatment.
• Measurable disease per IWG 2007 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status less than (\<) 2.
• Life expectancy of greater than (\>) 3 months.
• Adequate organ function, including the following:
• 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).
• 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.
• Renal: creatinine clearance \>=60 milliliter per minute (mL/min).
• 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.

You may not qualify if:

• Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases.
• Known human immunodeficiency virus (HIV)-related malignancy.
• 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).
• 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.
• Known HIV positive, hepatitis B surface antigen positive or known or suspected active hepatitis C infection.
• 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.
• Participants with certain cardiovascular conditions are excluded.
• Major surgery within 14 days before the first dose of study drug or incomplete recovery from any complications from surgery.
• Systemic infection requiring parenteral antibiotic therapy or other serious infection (bacterial, fungal, or viral) within 21 days before the first dose of study drug.
• Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of TAK-659.
• 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.
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659.
• 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.

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (41)

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-1274, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Swedish Medical Oncology - Edmonds

Edmonds, Washington, 98026, United States

Location

Swedish Cancer Institute - Issaquah

Issaquah, Washington, 98029, United States

Location

Swedish Health Services

Seattle, Washington, 98104, United States

Location

University of Washington, Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Swedish First Hill Campus

Seattle, Washington, 98122, United States

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G2M9, Canada

Location

CHU de Quebec -Universite Laval-Hopital de L'Enfant Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Centre Hospitalier Regional de Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

Hopital Haut-Leveque

Pessac, Aquitaine, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

CHRU Clermont- Ferrand CHU Estaing

Clermont-Ferrand, Auvergne, 63000, France

Location

Centre Henri-Becquerel

Rouen, Haute-normandie, 76038, France

Location

Hopital Dupuytren

Limoges, Limousin, Lorraine, 87042, France

Location

Institut Paoli Calmettes Departement de Recherche Clinique et de l'Innovation

Marseille, Provence-Alpes-Côte d'Azur Region, 13009, France

Location

Hopital Necker-Enfants Malades

Paris, Île-de-France Region, 75015, France

Location

Hopital Saint Louis

Paris, Île-de-France Region, 75475, France

Location

Groupe Hospitalier - Hopitaux Universitaires Pitie-Salpetriere - Charles-Foix - Pitie-Salpetriere

Paris, Île-de-France Region, 75651, France

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero-Universitaria "Maggiore della Carita"

Novara, 28100, Italy

Location

Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine

Udine, 33100, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, England, B15 2GW, United Kingdom

Location

London North West Healthcare NHS Trust, Imperial College London

Harrow, England, HA1 3UJ, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, England, NW1 2BU, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

Newcastle Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

TAK-659

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2017
• First Posted: April 21, 2017
• Study Start: October 10, 2017
• Primary Completion: December 17, 2019
• Study Completion: December 17, 2019
• Last Updated: February 8, 2023
• Results First Posted: September 16, 2020

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

US (10); CA (3); ES (7); IT (6); FR (10); GB (5)