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

Lymphocytic Leukemia, Chronic Clinical Trial

Official title:

An Open-Label, Multicenter, Phase Ib Trial of GA101 (RO5072759) in Combination With Chemotherapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01300247
• Other study ID #: GAO4779g
• Secondary ID: GO01298
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2011
• Last updated: March 4, 2016
• Start date: June 2011
• Est. completion date: December 2015

Study information

• Verified date: March 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 2015
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphocytic Leukemia, Chronic

Intervention

Drug:
• Fludarabine
Intravenous repeating dose
• RO5072759
Intravenous repeating dose
• bendamustine
Intravenous repeating dose
• cyclophosphamide
Intravenous repeating dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical laboratory abnormalities		Up to 3 years	No
Primary	Incidence of adverse events		Up to 3 years	No
Primary	Incidence of human anti-human antibodies (HAHAs)		Up to 6 months after end of treatment	No
Primary	Nature of adverse events		Up to 3 years	No
Primary	Severity of adverse events		Up to 3 years	No
Secondary	Pharmacokinetic parameters derived from plasma concentration-time profiles of GA101 following administration		Up to Day 141	No
Secondary	Objective response rate		Up to 3 months after end of treatment	No
Secondary	Duration of response		Up to 3 years after end of treatment	No
Secondary	Progression free survival		Up to 3 years after end of treatment	No
Secondary	Overall survival, defined as the time from randomization until death from any cause		up to 3.5 years	No
Secondary	Pharmacodynamics: Peripheral blood B-cell depletion and recovery		Up to Day 141	No