A Study Comparing RO5072759 (GA101) 1000 mg Versus 2000 mg in Patients With Previously Untreated Chronic Lymphocytic Leukemia (GAGE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01414205
First received: August 10, 2011
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This open-label, multicenter, randomized study will compare the efficacy, safety and pharmacokinetics of RO5072759 (GA101) 1000 mg versus 2000 mg in patients with previously untreated chronic lymphocytic leukemia. The randomization scheme will ensure approximately equal sample sizes in the two treatment dose arms for the following stratification factors: 1) tumor burden at baseline (high or low); and 2) Rai stage at baseline (study entry; I/II or III/IV). Tumor burden will be assessed on the basis of the presence or absence of at least one nodal mass >/= 5 cm in the baseline computed tomography (CT) scan. Patients will be randomized to receive a maximum of 8 cycles of GA101: 1000mg intravenous (iv) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8 on 21 day cycles or maximum of 8 cycles of GA101 2000mg iv infusion, on days 1 (split dose 100 mg on Day 1, 900 mg on Day 2, 1000 mg on Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8 on 21 day cycles.


Condition Intervention Phase
Lymphocytic Leukemia, Chronic
Drug: Obinutuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Randomized Phase II Trial Comparing the Efficacy, Safety, and Pharmacokinetics of GA101 1000 mg Versus 2000 mg in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    ORR was defined as the percentage of participants with complete response (CR), CR with incomplete marrow recovery (Cri) or partial response (PR) as assessed by the investigator according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines two months after last treatment. CR required: blood lymphocytes < 4 x 10^9/Liter (L), absence of lymphadenopathy (≤ 1.5 centimeter (cm) in long axis by Computed Tomography), no hepatomegaly or splenomegaly, absence of disease, Neutrophils > 1.5 x 10^9/L, Platelets > 100 x 10^9/L, Hemoglobin >11 g/dL, bone marrow normal and lymphoid nodules absent. CRi was CR with incomplete marrow recovery. PR required: 50% decrease in peripheral blood lymphocyte count, 50% reduction in lymphadenopathy, 50% reduction of liver and/or spleen enlargement if enlarged at baseline, Neutrophils > 1.5 x 10^9/L or > 50% of pretreatment value, Platelets > 100 x 10^9/L or 50% of pretreatment value and Hemoglobin > 11 g/dL or > 50% of pretreatment value.


Secondary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: up to 3.5 years ] [ Designated as safety issue: No ]
    PFS was defined as the time from the randomization to the first occurrence of progression or death, whichever occurred first.

  • Duration of Response [ Time Frame: up to 3.5 years ] [ Designated as safety issue: No ]
    Duration of response was defined as the first occurrence of a documented, objective response until the first occurrence of relapse or progression or death from any cause.

  • Overall Survival (OS) [ Time Frame: up to 3.5 years ] [ Designated as safety issue: No ]
    OS was defined as the time from randomization until death from any cause.

  • Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years) ] [ Designated as safety issue: No ]

    An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. A SAE was any AE that was one of the following: fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product or considered a significant medical event by the investigator.

    Additional information about AEs can be found in the Adverse Event Section


  • Percentage of Participants With Adverse Events of Interest [ Time Frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years) ] [ Designated as safety issue: No ]
    Adverse Events of interest for this study were: serious infusion related reactions during or within 24 hours of infusion, serious neutropenia, serious infection, tumor lysis syndrome and Hepatitis B reactivation.

  • Percentage of Participants With Adverse Events Leading to Study Discontinuation [ Time Frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years) ] [ Designated as safety issue: No ]
    An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.

  • PK Parameter: Maximum Serum Concentration (Cmax) [ Time Frame: Day 148 (at end of infusion) ] [ Designated as safety issue: No ]
    Blood was collected for Pharmacokinetic (PK) Parameter Cmax after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).

  • PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt ) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ] [ Designated as safety issue: No ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in day times micrograms per milliliter (day*μg/mL).

  • PK Parameter: Clearance at Steady State (CLss) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ] [ Designated as safety issue: No ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLss is reported in milliliters per day (mL/day).

  • PK Parameter: Volume of Distribution at Steady State (Vss) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ] [ Designated as safety issue: No ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Vss is reported in liters.

  • PK Parameter: Terminal Half-Life (t1/2) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ] [ Designated as safety issue: No ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). T1/2 was reported in Days.

  • Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion [ Time Frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years) ] [ Designated as safety issue: No ]
    Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell depletion was defined as a CD19 result < 0.07 × 10^9/L after at least one dose of study drug has been administered.

  • Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery [ Time Frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years) ] [ Designated as safety issue: No ]
    Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell recovery was defined as a CD19 result ≥ 0.07 × 10^9/L, where CD19 was previously depleted. B-cell recovery was only considered possible following the last dose of study treatment. The number of participants with B-cell recovery from End of Treatment to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) [PD before B-cell recovery or PD within 45 days after recovery] or Recovery without PD. PD required one of the following: 50% increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50% increase in the longest diameter of any previous site of lymphadenopathy, 50% increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology.


Enrollment: 80
Study Start Date: October 2011
Estimated Study Completion Date: March 2016
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Obinutuzumab 1000 mg
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Drug: Obinutuzumab
Obinutuzumab (RO5072759) Repeating intravenous dose.
Other Name: RO5072759
Experimental: Obinutuzumab 2000 mg
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Drug: Obinutuzumab
Obinutuzumab (RO5072759) Repeating intravenous dose.
Other Name: RO5072759

  Eligibility

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

Inclusion Criteria:

  • Cluster of differentiation antigen 20 (CD20)-positive B-cell chronic lymphocytic leukemia [per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines]
  • Rai Stage III/IV or Binet Stage C disease, or Rai Stage I/II or Binet Stage B disease that requires treatment according to IWCLL guidelines
  • No previous treatment for CLL chemotherapy, radiotherapy or immunotherapy; no previous rituximab treatment for autoimmune hemolytic anemia (AIHA) or Idiopathic thrombocytopenic purpura (ITP); prior use of steroids for AIHA or ITP is allowed
  • Eastern Cooperative Oncology Group performance status of 0, 1 or 2

Exclusion Criteria:

  • Transformation of CLL to aggressive B-cell malignancy
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  • Evidence of severe, uncontrolled concomitant disease
  • Known active infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks before the start of Cycle 1
  • Seropositive for human immunodeficiency virus (HIV)
  • Positive for chronic hepatitis B infection (defined as positive HBsAg serology)
  • Positive for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
  • Pregnant or lactating women
  • Concurrent (or within 7 days prior to fist dose of study treatment) systemic corticosteroid use, except for low-dose corticosteroid therapy used to treat 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: NCT01414205

  Show 35 Study Locations
Sponsors and Collaborators
Genentech
Investigators
Study Director: Jamie Hirata, Pharm.D Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01414205     History of Changes
Other Study ID Numbers: GAO4768g, GO25677
Study First Received: August 10, 2011
Results First Received: March 21, 2014
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Obinutuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014