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Trial record 1 of 1 for:    BTCT4465A
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A Safety and Pharmacokinetic Study of BTCT4465A, With or Without Single-dose Obinutuzumab Pretreatment, in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02500407
First received: July 14, 2015
Last updated: March 16, 2017
Last verified: March 2017
  Purpose
This study is designed to evaluate the safety and pharmacokinetics of BTCT4465A when administered as a single agent by intravenous (IV) infusion to participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Condition Intervention Phase
Lymphocytic Leukemia, Chronic
Lymphoma, Non Hodgkin
Drug: BTCT4465A
Drug: Obinutuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase I Trial Evaluating the Safety and Pharmacokinetics of Escalating Doses of BTCT4465A, With or Without Single-dose Obinutuzumab Pretreatment, in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: During Cycle 1 (up to 21 days; cycle length = 21 days) ]
  • Maximum Tolerated Dose (MTD) of BTCT4465A [ Time Frame: During Cycle 1 (up to 21 days; cycle length = 21 days) ]
  • Recommended Phase II Dose (RP2D) of BTCT4465A [ Time Frame: During Cycle 1 (up to 21 days; cycle length = 21 days) ]
  • Percentage of Participants With Adverse Events [ Time Frame: From Cycle 1 Day 1 until 90 days after the last infusion (cycle length = 21 days; up to approximately 9 months) ]
  • Area Under the Concentration-time Curve (AUC) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 of Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) [detailed time frame is provided in outcome measure description] ]
    0-4 hours (hr) before infusion, at the end of infusion (within 30 minutes; infusion duration=2 to 4 hr), 2, 24, 48, 72 hr post-infusion on Cycle 1 Day 1; Cycle 1 Days 8 and 15; 0-4 hr before infusion and at the end of infusion (within 30 minutes) on Day 1 of Cycles 2, 4, 6, and 8; Day 8 of Cycles 2, 4, 6, and 8; within 30 days after the last infusion (cycle length = 21 days; up to approximately 7 months)

  • Maximum Serum Concentration (Cmax) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 of Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) [detailed time frame is provided in outcome measure description] ]
    0-4 hr before infusion, at the end of infusion (within 30 minutes; infusion duration=2 to 4 hr), 2, 24, 48, 72 hr post-infusion on Cycle 1 Day 1; Cycle 1 Days 8 and 15; 0-4 hr before infusion and at the end of infusion (within 30 minutes) on Day 1 of Cycles 2, 4, 6, and 8; Day 8 of Cycles 2, 4, 6, and 8; within 30 days after the last infusion (cycle length = 21 days; up to approximately 7 months)

  • Minimum Serum Concentration (Cmin) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 of Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) [detailed time frame is provided in outcome measure description] ]
    0-4 hr before infusion, at the end of infusion (within 30 minutes; infusion duration=2 to 4 hr), 2, 24, 48, 72 hr post-infusion on Cycle 1 Day 1; Cycle 1 Days 8 and 15; 0-4 hr before infusion and at the end of infusion (within 30 minutes) on Day 1 of Cycles 2, 4, 6, and 8; Day 8 of Cycles 2, 4, 6, and 8; within 30 days after the last infusion (cycle length = 21 days; up to approximately 7 months)

  • Clearance (CL) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 of Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) [detailed time frame is provided in outcome measure description] ]
    0-4 hr before infusion, at the end of infusion (within 30 minutes; infusion duration=2 to 4 hr), 2, 24, 48, 72 hr post-infusion on Cycle 1 Day 1; Cycle 1 Days 8 and 15; 0-4 hr before infusion and at the end of infusion (within 30 minutes) on Day 1 of Cycles 2, 4, 6, and 8; Day 8 of Cycles 2, 4, 6, and 8; within 30 days after the last infusion (cycle length = 21 days; up to approximately 7 months)

  • Volume of Distribution at Steady State (Vss) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 of Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) [detailed time frame is provided in outcome measure description] ]
    0-4 hr before infusion, at the end of infusion (within 30 minutes; infusion duration=2 to 4 hr), 2, 24, 48, 72 hr post-infusion on Cycle 1 Day 1; Cycle 1 Days 8 and 15; 0-4 hr before infusion and at the end of infusion (within 30 minutes) on Day 1 of Cycles 2, 4, 6, and 8; Day 8 of Cycles 2, 4, 6, and 8; within 30 days after the last infusion (cycle length = 21 days; up to approximately 7 months)

  • AUC of Obinutuzumab [ Time Frame: 0-4 hours prior to BTCT4465A infusion on Cycle 1 Day 1 (cycle length = 21 days) ]
  • Cmax of Obinutuzumab [ Time Frame: 0-4 hours prior to BTCT4465A infusion on Cycle 1 Day 1 (cycle length = 21 days) ]
  • Cmin of Obinutuzumab [ Time Frame: 0-4 hours prior to BTCT4465A infusion on Cycle 1 Day 1 (cycle length = 21 days) ]
  • Clearance (CL) of Obinutuzumab [ Time Frame: 0-4 hours prior to BTCT4465A infusion on Cycle 1 Day 1 (cycle length = 21 days) ]
  • Vss of Obinutuzumab [ Time Frame: 0-4 hours prior to BTCT4465A infusion on Cycle 1 Day 1 (cycle length = 21 days) ]

Secondary Outcome Measures:
  • Percentage of Participants With Objective Response as Assessed by the Investigator Using Standard Criteria for NHL (Cheson 2007) and CLL (Hallek 2008) [ Time Frame: Screening, 6 weeks after first BTCT4465A infusion, then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]
  • Duration of Objective Tumor Response as Assessed by the Investigator Using Standard Criteria for NHL (Cheson 2007) and CLL (Hallek 2008) [ Time Frame: Screening, 6 weeks after first BTCT4465A infusion, then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]
  • Progression-free Survival (PFS) as Assessed by the Investigator Using Standard Criteria for NHL (Cheson 2007) and CLL (Hallek 2008) [ Time Frame: Screening, 6 weeks after first BTCT4465A infusion, then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]
  • Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to BTCT4465A [ Time Frame: Screening, 6 weeks after first BTCT4465A infusion, then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]

Estimated Enrollment: 210
Actual Study Start Date: September 30, 2015
Estimated Study Completion Date: October 31, 2018
Estimated Primary Completion Date: October 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BTCT4465A: Dose Escalation
Participants will receive BTCT4465A via IV infusion on Day 1 of each 21-day cycle (Groups A and C) or on Days 1, 8, and 15 of Cycle 1 and thereafter on Day 1 of each 21-day cycle (Group B) until disease progression or unacceptable toxicity for a maximum of 8 cycles. Dose escalation will be guided by the observed incidence of DLTs at each dose level. Three dose-escalation groups may be enrolled: Group A (Cycle 1 non-fractionated single-agent BTCT4465A escalation), Group B (Cycle 1 double-step fractionated single-agent BTCT4465A escalation), and Group C (Cycle 1 non-fractionated single-agent BTCT4465A escalation following pretreatment with a single dose of obinutuzumab).
Drug: BTCT4465A
Participants with B-cell NHL and CLL will receive BTCT4465A via IV infusion on Day 1 of each 21-day cycle (Groups A and C) or on Days 1, 8, and 15 of Cycle 1 and thereafter on Day 1 of each 21-day cycle (Group B) until disease progression or unacceptable toxicity for a maximum of 8 cycles.
Drug: Obinutuzumab
A single pretreatment dose of obinutuzumab will be administered intravenously 7 days prior to the first dose of BTCT4465A.
Other Name: Gazyva; Gazyvaro
Experimental: BTCT4465A: Dose Expansion
Participants will receive BTCT4465A with/without obinutuzumab pretreatment at the RP2D based on findings during dose escalation. BTCT4465A will be administered in 21-day cycles until disease progression or unacceptable toxicity for a maximum of 8 cycles.
Drug: BTCT4465A
Participants with B-cell NHL and CLL will receive BTCT4465A via IV infusion on Day 1 of each 21-day cycle (Groups A and C) or on Days 1, 8, and 15 of Cycle 1 and thereafter on Day 1 of each 21-day cycle (Group B) until disease progression or unacceptable toxicity for a maximum of 8 cycles.
Drug: Obinutuzumab
A single pretreatment dose of obinutuzumab will be administered intravenously 7 days prior to the first dose of BTCT4465A.
Other Name: Gazyva; Gazyvaro

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy at least 12 weeks
  • Dose-escalation stage: Grade 1 to 3b follicular lymphoma (FL), marginal zone lymphoma (MZL), transformed FL, Richter's transformation, diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), or CLL
  • Dose-expansion stage: DLBCL, transformed FL, Grade 1 to 3a FL, MZL, or CLL
  • Adverse events from prior anti-cancer therapy resolved to Grade 1 or better
  • Adequate hepatic, hematologic, and renal function
  • For participants and partners of childbearing potential, agreement to remain abstinent or utilize effective contraception

Exclusion Criteria:

  • Pregnant or lactating women
  • Monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, radiotherapy, chemotherapy, or other investigational anti-cancer agent within 4 weeks prior to study drug
  • Systemic immunotherapy within 12 weeks or 5 half-lives of drug prior to study drug
  • Systemic immunosuppressive medication within 2 weeks prior to study drug
  • Autologous stem cell transplantation (SCT) within 100 days prior to study drug, or any prior allogeneic SCT or solid organ transplantation
  • Autoimmune disease with the exception of controlled/treated hypothyroidism, disease-related immune thrombocytopenic purpura, or hemolytic anemia
  • History of confirmed progressive multifocal leukoencephalopathy (PML)
  • History of central nervous system (CNS) lymphoma or other CNS disease
  • Significant cardiovascular or pulmonary disease
  • Current infection, or prior infection requiring IV antibiotics and/or hospitalization within 4 weeks prior to study drug
  • Major surgery within 4 weeks prior to study drug
  • Hepatitis B or C or human immunodeficiency virus (HIV)
  • Receipt of a live attenuated vaccine within 4 weeks prior to study drug
  • History of drug or alcohol abuse within 12 weeks prior to Screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02500407

Contacts
Contact: Reference Study ID Number: GO29781 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
University of California San Diego Moores Cancer Center Not yet recruiting
La Jolla, California, United States, 92037
United States, Connecticut
Yale University School Of Medicine Recruiting
New Haven, Connecticut, United States, 06510
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
University of Pennsylvania; School of Medicine Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Australia, Victoria
Peter MacCallum Cancer Centre-East Melbourne Not yet recruiting
Melbourne, Victoria, Australia, 3000
Canada, British Columbia
BC Cancer Agency Vancouver Centre - PARENT Recruiting
Vancouver, British Columbia, Canada, V5Z 1H3
Canada, Ontario
Princess Margaret Hospital; Department of Med Oncology Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital; Research Unit Not yet recruiting
Montréal, Quebec, Canada, H3T 1E2
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02500407     History of Changes
Other Study ID Numbers: GO29781
Study First Received: July 14, 2015
Last Updated: March 16, 2017

Additional relevant MeSH terms:
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Obinutuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 21, 2017