Lymphoma, Non-Hodgkin
Conditions
Interventions
investigational material(s)
Generic name etc : TAK-659
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. To be enrolled to the dose escalation part, participants must have histologically or cytologically confirmed diagnosis of NHL for which no effective standard treatment is available. 2. To be enrolled in the expansion part, participants must meet the following criteria: a. Must have pathologically confirmed FL (Grade 1, 2, or 3A) or MZL. b. Relapsed and/or refractory to >=2 prior lines of chemotherapy based on standard of care that include at least 1 anti-CD20-based regimen, as well as alkylating agents (example cyclophosphamide or bendamustine). c. Participants must be ineligible for or refusal to hematopoietic stem cell transplant. d. If the participants have relapsed or progressed after achieving a response (defined as CR or PR), documented, investigator-assessed relapse or progression after the last treatment is required. 3. Measurable disease per IWG 2007 criteria. 4. Eastern Cooperative Oncology Group performance status score of 0 or 1. 5. Life expectancy of longer than 3 months. 6. Adequate organ function, including the following: a. Bone marrow reserve: absolute neutrophil count >=1,000 per cubic millimeter (/mm^3), platelet count >=75,000/mm^3 (>=50,000/mm^3 for participants with bone marrow involvement), and hemoglobin >=8 gram per deciliter (g/dL) (red blood cell [RBC] and platelet transfusion allowed >=14 days before assessment). b. Hepatic function: total bilirubin less than or equal to (=60 milliliter per minute (mL/min) either as estimated by the Cockcroft-Gault equation.
Exclusion criteria
Exclusion criteria: 1. Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases as indicated by positive cytology from lumbar puncture or computed tomography (CT)/magnetic resonance imaging (MRI) by local assessment. 2. 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, antibodydrug conjugate, and bi-specific T-cell engager agent; <=8 weeks for cellbased therapy or anti-tumor vaccine). 3. Radiotherapy less than (<) 3 weeks before the first dose of study treatment. If prior radiotherapy occurred <4 to 6 weeks before the study start, as radiated lesions cannot be reliably assessed by fluoro-2-deoxy- D-glucose (FDG)-positron emission tomography (PET), nonradiated target lesions are required for eligibility. 4. 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 at any time. 5. Any clinically significant comorbidities, such as uncontrolled pulmonary disease (example, severe chronic obstructive pulmonary disease with hypoxemia, interstitial lung disease, radiation induced lung injury), known impaired cardiac function or clinically significant cardiac disease, active CNS disease, or any other condition that could, in the opinion of the investigator, compromise the participant's safety and participation in the study per protocol. 6. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659. 7. Use or consumption of any of the following substances: 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 time frame 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 halflife (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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Timeframe; From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) safety Percentage of Participants With Grade 3 or Higher TEAEs Timeframe; From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]). safety Percentage of Participants With Serious TEAEs Timeframe; From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) safety Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 Timeframe; Cycle 1 (Cycle length =28 days) safety Percentage of Participants who Discontinued Study Drug due to TEAEs Timeframe; From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) pharmacokinetics Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1 Time Frame; pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) pharmacokinetics Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cyc | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Expansion Part: Overall Response Rate (ORR) Timeframe; Up to 52 months The percentage of participants in the response-evaluable population of the expansion part who achieved either complete remission (CR) or partial remission (PR), as assessed by investigators, according to modified International Working Group (IWG) criteria for malignant lymphoma. CR is defined as disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. efficacy Expansion Part: CR Rate Timeframe; Up to 52 months The percentage of participants in the response-evaluable population of the expansion part who achieved CR, as assessed by investigator, according to modified IWG criteria for malignant lymphoma. CR is defined as disappearance of all evidence of disease. efficacy Expansion Part: Duration of Response (DOR) Timeframe; Up to 52 months The time from first documentation of response (CR/PR) to the date of first documentation of PD/relapse, as assessed by investigator, according to modified IWG criteria for malignant lymphoma in the response-evaluable population of the expansion part. CR is defined as disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. Progressive disease (PD) is defined as any new lesion or increase by greater than or equal to (>=) 50 percent (%) of previously involved sites from nadir. efficacy Expansion Part: Progression-free Survival (PFS) Timeframe; Up to 52 months The time from the date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurs first, in the safety population of the expansion part, as assessed by the investigator, according to modified IWG criteria for malignant lymphoma. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. | — |
Countries
Japan, Republic of Korea
Outcome results
None listed