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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: TAK-659

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Quebec -Universite Laval-Hopital de L'Enfant Jesus
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Center
  • Quebec
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre Hospitalier Regional De Rimouski
• France
  • Aquitaine
    • Pessac Cedex, Aquitaine, France, 33604
      • Hôpital Haut-Lévèque
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63000
      • CHRU Clermont- Ferrand CHU Estaing
  • Haute-normandie
    • Rouen Cedex 1, Haute-normandie, France, 76038
      • Centre Henri-Becquerel
  • Ile-de-france
    • Paris, Ile-de-france, France, 75015
      • Hôpital Necker-Enfants Malades
    • Paris Cedex 10, Ile-de-france, France, 75475
      • Hôpital Saint louis
    • Paris Cedex 13, Ile-de-france, France, 75651
      • Groupe Hospitalier - Hopitaux Universitaires Pitie-Salpetriere - Charles-Foix - Pitie-Salpetriere
    • Villejuif Cedex, Ile-de-france, France, 94805
      • Institut Gustave Roussy
  • Limousin, Lorraine
    • Limoges Cedex, Limousin, Lorraine, France, 87042
      • Hôpital Dupuytren
  • Provence Alpes COTE D'azur
    • Marseille, Provence Alpes COTE D'azur, France, 13009
      • Institut Paoli Calmettes Departement de Recherche Clinique et de l'Innovation
  • Rhone-alpes
    • Pierre Benite Cedex, Rhone-alpes, France, 69495
      • Centre Hospitalier Lyon Sud
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Milano, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Novara, Italy, 28100
    • Azienda Ospedaliero-Universitaria "Maggiore della Carità"
  • Udine, Italy, 33100
    • Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • Ospedale Casa Sollievo della Sofferenza
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2GW
      • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
    • Harrow, England, United Kingdom, HA1 3UJ
      • London North West Healthcare NHS Trust, Imperial College London
    • London, England, United Kingdom, NW1 2BU
      • University College London Hospitals NHS Foundation Trust
    • Manchester, England, United Kingdom, M20 4BX
      • The Christie NHS Foundation Trust
    • Newcastle upon Tyne, England, United Kingdom, NE7 7DN
      • Newcastle Hospitals NHS Foundation Trust
• United States
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-1274
      • University of Michigan
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
  • Washington
    • Edmonds, Washington, United States, 98026
      • Swedish Medical Oncology - Edmonds
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute - Issaquah
    • Seattle, Washington, United States, 98104
      • Swedish Health Services
    • Seattle, Washington, United States, 98109
      • University of Washington, Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98122
      • Swedish First Hill Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	Drug: TAK-659; TAK-659 Tablets
EXPERIMENTAL: 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).	Drug: TAK-659; TAK-659 Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria	CR rate was defined as percentage of participants with complete response as assessed by IRC according to the modified 2007 IWG. CR was defined as disappearance of all evidence of disease.	Up to 12 months
Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria	ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the 2014 Lugano classification, 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
Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria	CR rate was defined as percentage of participants with complete response as assessed by IRC according to the 2014 Lugano classification, IWG criteria. CR was defined as disappearance of all evidence of disease.	Up to 12 months
Stage 2: Duration of Response (DOR)	DOR was 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 IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.	Up to 12 months
Stage 2: Duration of CR	Duration of CR was 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 IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.	Up to 12 months
Stage 2: ORR as Assessed by IRRC in Participants With Germinal Center B-cell (GCB) DLBCL	ORR was defined as the percentage of participants with CR or 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
Stage 2: ORR as Assessed by IRC in Participants With DLBCL Transformed From Indolent Non-Hodgkin's Lymphoma (NHL)	ORR was defined as the percentage of participants with CR or PR as assessed by IRC 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
Stage 2: Progression Free Survival (PFS) as Assessed by IRC	PFS was 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. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.	Up to 18 months
Stage 2: Overall Survival (OS)	OS was defined as the time from start of study treatment to date of death due to any cause.	Up to 24 months
Stage 1: ORR as Assessed by IRRC to Select Stage 2 Dose Regimen of TAK-659 From the Lead-in Dose Exploration Phase	ORR was defined as the percentage of participants with CR or PR as assessed by IRC. 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
Stage 2: ORR as Assessed by IRC at 3, 6, and 9 Cycles in Participants With DLBCL	ORR was defined as the percentage of participants with CR or PR as assessed by IRC 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.	At Cycles 3, 6 and 9 (Up to 12 months) (Each cycle of 28 days)

Collaborators and Investigators

• Sponsor: Calithera Biosciences, Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 10, 2017
• Primary Completion (ACTUAL): December 17, 2019
• Study Completion (ACTUAL): December 17, 2019

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (ACTUAL): April 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: C34004; U1111-1187-6208 (OTHER: WHO); 2016-003716-12 (EUDRACT_NUMBER); 17/YH/0181 (REGISTRY: NRES)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No