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

NCT ID: NCT03123393

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-10
• Study Completion Date: 2019-12-17

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.

Detailed Description

The drug being tested is TAK-659. This study will evaluate overall response rate (ORR) 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 a 28-day cycle.

This multi-center trial will be conducted in the 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 every 3 months after end of treatment (for participants who discontinue due to reasons other than disease progression) and OS follow-up every 3 months from the last dose of study drug until death or conclusion of the study, whichever occurs first.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: TAK-659 100 mg

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

Group Type: EXPERIMENTAL

TAK-659

Intervention Type: DRUG

TAK-659 Tablets

Cohort B: TAK-659 Ramp-up Dosing

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

Group Type: EXPERIMENTAL

TAK-659

Intervention Type: DRUG

TAK-659 Tablets

Interventions

TAK-659

TAK-659 Tablets

Intervention Type: DRUG

Eligibility 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 antihyperglycemic 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

University of Kansas Medical Center

Westwood, Kansas, United States

University of Michigan

Ann Arbor, Michigan, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York University Langone Medical Center

New York, New York, United States

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Swedish Medical Oncology - Edmonds

Edmonds, Washington, United States

Swedish Cancer Institute - Issaquah

Issaquah, Washington, United States

Swedish Health Services

Seattle, Washington, United States

University of Washington, Hutchinson Cancer Research Center

Seattle, Washington, United States

Swedish First Hill Campus

Seattle, Washington, United States

Princess Margaret Cancer Center

Toronto, Ontario, Canada

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

Québec, Quebec, Canada

Centre Hospitalier Regional de Rimouski

Rimouski, Quebec, Canada

Hopital Haut-Leveque

Pessac, Aquitaine, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

CHRU Clermont- Ferrand CHU Estaing

Clermont-Ferrand, Auvergne, France

Centre Henri-Becquerel

Rouen, Haute-normandie, France

Hopital Dupuytren

Limoges, Limousin, Lorraine, France

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

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

Hopital Necker-Enfants Malades

Paris, Île-de-France Region, France

Hopital Saint Louis

Paris, Île-de-France Region, France

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

Paris, Île-de-France Region, France

Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliero-Universitaria "Maggiore della Carita"

Novara, , Italy

Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine

Udine, , Italy

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Hospital Universitario La Fe

Valencia, , Spain

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, England, United Kingdom

London North West Healthcare NHS Trust, Imperial College London

Harrow, England, United Kingdom

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom

The Christie NHS Foundation Trust

Manchester, England, United Kingdom

Newcastle Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, United Kingdom

Countries

United States; Canada; France; Italy; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1187-6208

Identifier Type: OTHER

Identifier Source: secondary_id

2016-003716-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17/YH/0181

Identifier Type: REGISTRY

Identifier Source: secondary_id

C34004

Identifier Type: -

Identifier Source: org_study_id