A Study of GA101 (RO5072759) in Combination With Chemotherapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia (GALTON)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01300247
First received: February 14, 2011
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

This open-label, 2-arm, nonrandomized, multicenter, Phase Ib study will investigate the safety and efficacy of RO5072759 (GA101) administered in combination with chemotherapy (bendamustine or FC regimens) in patients with previously untreated CD20-positive B-CLL. Patients will be enrolled to receive a maximum of 6 cycles of GA101 (1000mg iv infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2 - 6) plus bendamustine (90 mg/m2 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 GA101 (1000mg iv infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2 - 6) plus FC (fludarabine 25 mg/m2 IV on days 2, 3 and 4 of cycle 1 and days 1, 2 and 3 of cycles 2 - 6; cyclophosphamide 250 mg/m2 IV on days 2, 3 and 4 of cycle 1 and days 1, 2 and 3 of cycles 2 - 6) on 28 day cycles.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: bendamustine
Drug: cyclophosphamide
Drug: Fludarabine
Drug: RO5072759
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase Ib Trial of GA101 (RO5072759) in Combination With Chemotherapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Clinical laboratory abnormalities [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of human anti-human antibodies (HAHAs) [ Time Frame: Up to 6 months after end of treatment ] [ Designated as safety issue: No ]
  • Nature of adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Severity of adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters derived from plasma concentration-time profiles of GA101 following administration [ Time Frame: Up to Day 141 ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: Up to 3 months after end of treatment ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 3 years after end of treatment ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: Up to 3 years after end of treatment ] [ Designated as safety issue: No ]
  • Overall survival, defined as the time from randomization until death from any cause [ Time Frame: up to 3.5 years ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Peripheral blood B-cell depletion and recovery [ Time Frame: Up to Day 141 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: June 2011
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: bendamustine
Intravenous repeating dose
Drug: RO5072759
Intravenous repeating dose
Experimental: B Drug: cyclophosphamide
Intravenous repeating dose
Drug: Fludarabine
Intravenous repeating dose
Drug: RO5072759
Intravenous repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • ECOG performance status of 0, 1, or 2
  • Life expectancy of > 6 months

Exclusion Criteria:

  • 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 =< 60 mL/min, calculated according to the formula of Cockroft and Gault
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN)
  • Total bilirubin >= 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
  • Presence of positive test results for hepatitis B (hepatitis B virus [HBV] surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C (hepatitis C virus [HCV] antibody serology testing). Patients with chronic HBV infection, occult HBV infection, or past HBV infection will be excluded. Patients who have received IVIG within 3 months of enrollment and who are anti-HBc positive but HBV DNA negative will be considered for inclusion on the study by the Medical Monitor on a case-by-case basis. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • 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
  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: NCT01300247

Locations
United States, Alabama
Huntsville, Alabama, United States, 35805
United States, California
Duarte, California, United States, 91010
La Jolla, California, United States, 92093
Los Angeles, California, United States, 90095
United States, Connecticut
Southington, Connecticut, United States, 06489
United States, Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
Atlanta, Georgia, United States, 30322
Marietta, Georgia, United States, 30060
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Maryland
Boston, Maryland, United States, 02115
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Minnesota
St. Louis Park, Minnesota, United States, 55426
United States, Missouri
Springfield, Missouri, United States, 65807
United States, New York
Rochester, New York, United States, 14642
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98109
Tacoma, Washington, United States, 98405
United States, Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Genentech
Investigators
Study Director: Jamie Hirata, Pharm.D. Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01300247     History of Changes
Other Study ID Numbers: GAO4779g, GO01298
Study First Received: February 14, 2011
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Bendamustine
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 28, 2014