A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)

NCT01300247 | Completed Phase 1 Results DMC

• 2 other identifiers: GAO4779gGO01298
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 18

Brief Summary

This open-label, 2-arm, nonrandomized, multicenter, Phase Ib study will investigate the safety and efficacy of obinutuzumab (RO5072759; GA101) administered in combination with chemotherapy (bendamustine or fludarabine + cyclophosphamide \[FC\] regimens) in participants with previously untreated cluster of differentiation 20 (CD20)-positive B-CLL. Participants will be enrolled to receive a maximum of 6 cycles of obinutuzumab (1000 milligrams \[mg\] intravenous \[IV\] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus bendamustine (90 milligrams per meter square \[mg/m\^2\] IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2 - 6) on 28 day cycles or a maximum of 6 cycles of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus FC (fludarabine 25 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2 - 6; cyclophosphamide 250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2 - 6) on 28 day cycles.

Conditions

Lymphocytic Leukemia, Chronic

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Human Anti-Human Antibodies (HAHAs)

  Cycle 1 Day 1 (cycle length = 28 days) up to clinical data cutoff date 24 January 2013 (up to approximately 1.75 years)

Secondary Outcomes (12)

• Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab

  Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

• Maximum Plasma Concentration (Cmax) of Obinutuzumab

  Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

• Trough Plasma Concentration (Ctrough) of Obinutuzumab

  Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1

• Clearance of Obinutuzumab

  Pre-dose on C1D1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

• Volume of Distribution of Obinutuzumab

  Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

Study Arms (2)

Obinutuzumab + Fludarabine + Cyclophosphamide

EXPERIMENTAL

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6), and cyclophosphamide (250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6).

Drug: Fludarabine; Drug: Obinutuzumab; Drug: Cyclophosphamide

Obinutuzumab + Bendamustine

EXPERIMENTAL

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).

Drug: Obinutuzumab; Drug: Bendamustine

Interventions

Fludarabine DRUG

Participants will receive 6 cycles (each 28-day cycle) of fludarabine at dose of 25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Obinutuzumab + Fludarabine + Cyclophosphamide

Obinutuzumab DRUG

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.

Also known as: RO5072759; GA101

Obinutuzumab + Bendamustine; Obinutuzumab + Fludarabine + Cyclophosphamide

Bendamustine DRUG

Participants will receive 6 cycles (each 28-day cycle) of bendamustine at dose of 90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.

Obinutuzumab + Bendamustine

Cyclophosphamide DRUG

Participants will receive 6 cycles (each 28-day cycle) of cyclophosphamide at dose of 250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Obinutuzumab + Fludarabine + Cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of CD20-positive B-CLL
• Rai Stage III/IV or Binet Stage C disease
• Rai Stage I/II or Binet Stage B disease that requires treatment
• Adequate baseline bone marrow function, unless there is clear evidence of extensive bone marrow involvement with tumor infiltration, myelodysplasia, or hypocellularity
• No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of greater than (\>) 6 months

You may not qualify if:

• Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to the start of Cycle 1
• Transformation of CLL to aggressive B-cell malignancy
• Creatinine clearance less than equal to (\<=) 60 milliliters per minute (mL/min), calculated according to the formula of Cockcroft and Gault
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5 times the upper limit of normal (ULN)
• Total bilirubin greater than equal to (\>=) 3 x ULN
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• History of sensitivity to mannitol (if bendamustine is to be administered)
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease
• Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1
• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Known infection with human immunodeficiency virus (HIV) seropositive status
• Women who are pregnant or lactating
• Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly
• Concurrent (or within 7 days prior to the first dose of study treatment) systemic corticosteroid use except low-dose corticosteroid therapy used to treat an illness other than lymphoma

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (18)

Unknown Facility

Huntsville, Alabama, 35805, United States

Location

Unknown Facility

Duarte, California, 91010, United States

Location

Unknown Facility

La Jolla, California, 92093, United States

Location

Unknown Facility

Los Angeles, California, 90095, United States

Location

Unknown Facility

Southington, Connecticut, 06489, United States

Location

Unknown Facility

Tampa, Florida, 33612-9497, United States

Location

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Marietta, Georgia, 30060, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Boston, Maryland, 02115, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Saint Louis Park, Minnesota, 55426, United States

Location

Unknown Facility

Springfield, Missouri, 65807, United States

Location

Unknown Facility

Rochester, New York, 14642, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Seattle, Washington, 98109, United States

Location

Unknown Facility

Tacoma, Washington, 98405, United States

Location

Unknown Facility

Madison, Wisconsin, 53705, United States

Location

Related Publications (1)

• Brown JR, O'Brien S, Kingsley CD, Eradat H, Pagel JM, Lymp J, Hirata J, Kipps TJ. Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial. Blood. 2015 Apr 30;125(18):2779-85. doi: 10.1182/blood-2014-12-613570. Epub 2015 Mar 13.

  PMID: 25769620 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine; obinutuzumab; Bendamustine Hydrochloride; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

The interim data reported here (up to clinical cutoff date of 24 January 2013) were for participants who had completed treatment response assessment, which took place approximately 2 months after the last infusion of study treatment.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: February 21, 2011
• Study Start: May 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: December 1, 2015
• Last Updated: February 2, 2017
• Results First Posted: June 24, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)