Overview

This trial is active, not recruiting.

Condition chronic lymphocytic leukemia
Treatments bendamustine, chlorambucil, cyclophosphamide, fludarabine, obinutuzumab
Phase phase 3
Target CD20
Sponsor Hoffmann-La Roche
Start date November 2013
End date October 2018
Trial size 979 participants
Trial identifier NCT01905943, 2013-000087-29, MO28543

Summary

This multicenter, open-label, single-arm study will evaluate the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in participants with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL). Participants will receive 6 cycles of single-agent obinutuzumab or obinutuzumab in combination with chemotherapy at the investigator's discretion. Each participant will be followed until 30 months after the last participant has been enrolled. Total length of the study is anticipated to be approximately 5 years.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants will receive obinutuzumab 1000 mg IV infusion on Days 1/2 (dose split over 2 consecutive days; 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of Cycle 1, and on Day 1 of Cycles 2, 3, 4, 5, and 6 either alone as single agent, or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
bendamustine
Participants will receive bendamustine everyday (qd) on Days 1 to 2 of each 28-day cycle from Cycle 1 to Cycle 6 as per invetigator's discretion.
chlorambucil
Participants will receive clorambucil qd on Days 1 and 15 of each 28-day cycle from Cycle 1 to Cycle 6 as per invetigator's discretion.
cyclophosphamide
Participants will receive cyclophosphamide qd on Days 1 to 3 of each 28-day cycle from Cycle 1 to Cycle 6 as per invetigator's discretion.
fludarabine
Participants will receive fludarabine qd on Days 1 to 3 of each 28-day cycle from Cycle 1 to Cycle 6 as per invetigator's discretion.
obinutuzumab RO5072759
Participants will receive obinutuzumab 1000 mg IV infusion on Days 1/2 (dose split over 2 consecutive days; 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1, and on Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle is of 28-days duration.

Primary Outcomes

Measure
Number of participants with adverse events (AEs) and serious adverse events (SAEs) based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0)
time frame: Baseline up to end of study (Approximately 5 years)

Secondary Outcomes

Measure
Number of participants with minimal residual disease (MRD)-negativity as assessed by flow cytometry
time frame: 3 months after the last dose of study treatment (up to 5 years)
Percentage of participants with overall response as determined by the investigator
time frame: 3 months after the last dose of study treatment (up to 5 years)
Progression-free survival (PFS)
time frame: Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to 5 years total)
Time to response (TTR)
time frame: Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to 5 years total)
Event-free survival (EFS) as assessed by the investigator
time frame: Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to 5 years total)
Percentage of participants with best overall response (BOR) as determined by the investigator
time frame: Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to 5 years total)
Overall survival (OS)
time frame: Baseline until death (Approximately up to 5 years)
Time to new anti-leukemia therapy (TTNT)
time frame: Baseline until end of study (Approximately up to 5 years)
Duration of response (DoR)
time frame: Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to 5 years total)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Previously untreated documented CLL according to national cancer institute/international workshop on CLL (NCI/iwCLL) criteria OR relapsed and/or refractory documented CLL participants requiring treatment according to NCI/iwCLL criteria; participants with up to 3 relapses are eligible - Refractory participants if last treatment was with single-agent therapy, single-agent chemotherapy, or single-agent antibody - Participants with 17p-deletion and/or p53 mutation may be included at the investigator's discretion - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Life expectancy greater than (>) 6 months according to the investigator's opinion - Adequate hematological function Exclusion Criteria: - Participants who have received more than 3 previous CLL treatment lines - Documented transformation of CLL to aggressive lymphoma (Richter's transformation) - Participants who are refractory to immunochemotherapy - Participants with abnormal laboratory values - One or more individual organ/system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition, excluding the eyes, ears, nose, throat and larynx organ system - Participants with a history of progressive multifocal leukoencephalopathy (PML) - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy - Known hypersensitivity to the study drugs - History of prior malignancy unless the malignancy has been treated with a curative intent and in remission without treatment for greater than or equal to (>/=) 5 years prior to enrollment and with the exception of curatively-treated basal cell carcinoma, squamous cell carcinoma of the skin, low grade in situ carcinoma of the cervix, or low grade, early stage localized prostate cancer treated surgically with curative intent - Regular treatment with corticosteroids during the 28 days prior to the start of Cycle 1, Day 1, unless administered for indications other than CLL at a dose equivalent to less than or equal to (

Additional Information

Official title A Multicenter, Open-Label, Single-Arm, Phase IIIb, International Study Evaluating the Safety of Abinutuzumab Alone or in Combination With Chemotherapy in Patients With Previously Untreated or Relapsed/Refractory Chronic Lymphocytic Leukemia
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.