A Study of TAK-659 in Combination With Bendamustine (+/-Rituximab), Gemcitabine, Lenalidomide, or Ibrutinib for the Treatment of Participants With Advanced Non-Hodgkin Lymphoma

Conditions

• Lymphoma, Non-Hodgkin

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• TAK-659 — DRUG
  TAK-659 immediate release tablet
• Bendamustine — DRUG
  Bendamustine intravenous infusion
• Rituximab — DRUG
  Rituximab intravenous infusion
• Gemcitabine — DRUG
  Gemcitabine intravenous infusion
• Lenalidomide — DRUG
  Lenalidomide capsule
• Ibrutinib — DRUG
  Ibrutinib capsule

Study Details

The purpose of this study is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of TAK-659 when administered in combination with bendamustine, bendamustine + rituximab, gemcitabine, lenalidomide, or ibrutinib.

Key Dates

Start date

Mar 5, 2017

Status verified

Dec 2021

Primary completion

Jul 27, 2020

Completion

Jul 27, 2020

Study Design

Enrollment

43 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2
  TAK-659 60 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with bendamustine 90 mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 in a 21-day treatment cycle, for up to 8 cycles. Participants continued to receive TAK-659 monotherapy until they experienced progressive disease (PD) or unacceptable toxicities or up to 39 cycles.
• Experimental: Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2
  TAK-659 80 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with bendamustine 90 mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 in a 21-day treatment cycle, for up to 8 cycles. The TAK-659 was escalated to 80 mg once daily after safety and tolerability of 60 mg dose was determined. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 39 cycles.
• Experimental: Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2
  TAK-659 100 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with bendamustine mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 in a 21-day treatment cycle, for up to 8 cycles. The TAK-659 was escalated to 100 mg once daily after safety and tolerability of 60 mg dose was determined. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 39 cycles.
• Experimental: Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2
  TAK-659 60 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with bendamustine 90 mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 along with rituximab 375 mg/m\^2, infusion, intravenously, on Day 1 in a 21-day treatment cycle, for up to 8 cycles. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 12 cycles.
• Experimental: Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2
  TAK-659 80 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with bendamustine 90 mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 along with rituximab 375 mg/m\^2, infusion, intravenously, on Day 1 in a 21-day treatment cycle, for up to 8 cycles. The TAK-659 was escalated to 80 mg once daily after safety and tolerability of 60 mg dose was determined. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 12 cycles.
• Experimental: Dose Escalation Phase Cohort B: TAK-659 100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2
  TAK-659 100 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with bendamustine 90 mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 along with rituximab 375 mg/m\^2, infusion, intravenously, on Day 1 in a 21-day treatment cycle, for up to 8 cycles. The TAK-659 was escalated to 100 mg once daily after safety and tolerability of 60 mg dose was determined. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 12 cycles.
• Experimental: Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2
  TAK-659 60 mg, immediate-release tablet, orally, once daily on Days 1 to 21 along with gemcitabine 1000 mg/m\^2, infusion, intravenously, over 30 minutes on Days 1 and 8 in a 21-day treatment cycle. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 2 cycles.
• Experimental: Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg
  TAK-659 40 mg, immediate-release tablet, orally, once daily on Days 1 to 28 along with lenalidomide 25 mg, capsules orally, once daily on Days 1 to 21 in a 28-day treatment cycle. The TAK-659 60 mg dose was de-escalated to 40 mg in case of dose limiting toxicity or if the starting dose was determined to be not tolerable. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 26 cycles.
• Experimental: Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg
  TAK-659 60 mg, immediate-release tablet, orally, once daily on Days 1 to 28 along with lenalidomide 25 mg, capsules orally, once daily on Days 1 to 21 in a 28-day treatment cycle. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 26 cycles.
• Experimental: Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg
  TAK-659 60 mg, immediate-release tablet, orally, once daily along with ibrutinib 560 mg capsules, orally, once daily on Days 1 to 28 in a 28-day treatment cycle. Participants continued to receive TAK-659 monotherapy until they experienced PD or unacceptable toxicities or up to 3 cycles.
• Experimental: Safety Expansion Phase Cohort B: TAK-659 + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2
  TAK-659 immediate-release tablet, at the MTD/maximally administered dose (MAD)/RP2D determined from Dose Escalation Phase, orally, once daily on Days 1 to 21 along with bendamustine 90 mg/m\^2, infusion, intravenously, over 10 or 60 minutes on Days 1 and 2 along with rituximab 375 mg/m\^2, infusion, intravenously, on Day 1 in a 21-day treatment cycle, for up to 8 cycles in participants (who were to be entered in Phase 2) with advanced FL or MZL. Treatment could then be continued until they experienced PD or unacceptable toxicities or up to 12 cycles in participants who were to be enrolled in the Safety Expansion Phase Cohort.

Primary Outcome Measure

Dose Escalation Phase: Maximum Tolerated Dose (MTD) of TAK-659 [ Time Frame: Cycle 1 (Cohorts A, B and C - each cycle was of 21 days and Cohorts D and E - each cycle was of 28 days) ]

Locations (11)

Find similar trials in Tucson, AZ

Related Studies

• Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma and Hodgkin's Disease
  Recruiting · Stanford University · Stanford, California
• Tissue Collection for Studies of Lymph Cancer
  Recruiting · National Cancer Institute (NCI) · Bethesda, Maryland
• Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols
  Recruiting · National Cancer Institute (NCI) · Bethesda, Maryland
• TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
  PHASE2 · Recruiting · American Society of Clinical Oncology · Birmingham, Alabama