Clinical trial NCT03123393: TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Drug therapy
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria
timeFrame: Up to 12 months
Secondary outcomes:
measure: Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria
timeFrame: Up to 12 months
measure: Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria
timeFrame: Up to 12 months
measure: Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria
timeFrame: Up to 12 months
measure: Stage 2: Duration of Response (DOR)
timeFrame: Up to 12 months
measure: Stage 2: Duration of CR
timeFrame: Up to 12 months
measure: Stage 2: ORR as Assessed by IRRC in Participants With Germinal Center B-cell (GCB) DLBCL
timeFrame: Up to 12 months
measure: Stage 2: ORR as Assessed by IRC in Participants With DLBCL Transformed From Indolent Non-Hodgkin's Lymphoma (NHL)
timeFrame: Up to 12 months
measure: Stage 2: Progression Free Survival (PFS) as Assessed by IRC
timeFrame: Up to 18 months
measure: Stage 2: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Stage 1: ORR as Assessed by IRRC to Select Stage 2 Dose Regimen of TAK-659 From the Lead-in Dose Exploration Phase
timeFrame: Up to 12 months
measure: Stage 2: ORR as Assessed by IRC at 3, 6, and 9 Cycles in Participants With DLBCL
timeFrame: At Cycles 3, 6 and 9 (Up to 12 months) (Each cycle of 28 days)
Other outcomes:
Locations:
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Edmonds
country: United States
facility: Swedish Medical Oncology - Edmonds
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute - Issaquah
state: Washington
city: Seattle
country: United States
facility: Swedish Health Services
state: Washington
city: Seattle
country: United States
facility: University of Washington, Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish First Hill Campus
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Rimouski
country: Canada
facility: Centre Hospitalier Regional de Rimouski
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec -Universite Laval-Hopital de L'Enfant Jesus
city: Pessac Cedex
country: France
facility: Hopital Haut-Leveque
state: Aquitaine
city: Clermont-Ferrand
country: France
facility: CHRU Clermont- Ferrand CHU Estaing
state: Auvergne
city: Rouen Cedex 1
country: France
facility: Centre Henri-Becquerel
state: Haute-normandie
city: Paris Cedex 10
country: France
facility: Hopital Saint Louis
state: Ile-de-france
city: Paris Cedex 13
country: France
facility: Groupe Hospitalier - Hopitaux Universitaires Pitie-Salpetriere - Charles-Foix - Pitie-Salpetriere
state: Ile-de-france
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
state: Ile-de-france
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Ile-de-france
city: Limoges Cedex
country: France
facility: Hopital Dupuytren
state: Limousin, Lorraine
city: Marseille
country: France
facility: Institut Paoli Calmettes Departement de Recherche Clinique et de l'Innovation
state: Provence Alpes COTE D'azur
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone-alpes
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza
state: Foggia
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
state: Piemonte
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria "Maggiore della Carita"
city: Udine
country: Italy
facility: Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
state: England
city: Harrow
country: United Kingdom
facility: London North West Healthcare NHS Trust, Imperial College London
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle Hospitals NHS Foundation Trust
state: England
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: