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Lymphocytic Leukemia, ChronicPhase 2NCT01414205

A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE)

A Phase 2 study testing Obinutuzumab and Corticosteroids in people with Lymphocytic Leukemia, Chronic, run by Genentech, Inc. at 31 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This open-label, multicenter, randomized study compared the efficacy, safety and pharmacokinetics of obinutuzumab (RO5072759; GA101) 1000 mg versus 2000 mg in participants with previously untreated CLL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphocytic Leukemia, Chronic
What is being tested?
Obinutuzumab and Corticosteroids
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
31 sitesUnited States
Study dates
31 Oct 2011to 31 Mar 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of CD20-positive B-cell CLL (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

Who cannot join

  • Confirmed diagnosis of 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 hepatitis B surface antigen [HBsAg] serology)
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  • Positive for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
  • Pregnant or lactating women
  • Concurrent (or within 7 days prior to first dose of study treatment) systemic corticosteroid use, except for low-dose corticosteroid therapy used to treat chronic medical conditions

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

United States31 sites

  • Univ of Colorado Canc Ctr

    Aurora, Colorado, 80045

  • Univ of Alabama at Birmingham; UAB Comprehensive Cancer Ctr

    Birmingham, Alabama, 35291-3300

  • Ohio State University

    Columbus, Ohio, 43210

  • Mark H. Zangmeister Center

    Columbus, Ohio, 43219

  • Texas Oncology-Medical City Dallas

    Dallas, Texas, 75230

  • Texas Oncology - Dallas Presbyterian Hospital

    Dallas, Texas, 75231

  • Rocky Mountain Cancer Center; Medical Oncology

    Denver, Colorado, 80218

  • Willamette Valley Cancer Ctr - 520 Country Club

    Eugene, Oregon, 97401-8122

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • US Oncology Research Pharm.

    Fort Worth, Texas, 76177

  • Goshen Hlth Sys Ctr Can Care

    Goshen, Indiana, 46526

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • University of California; Moores Cancer Center

    La Jolla, California, 92093

  • Horizon Oncology Research, Inc.

    Lafayette, Indiana, 47905

  • USC Norris Cancer Center

    Los Angeles, California, 90033

  • USC/Norris Can Ctr; IDS Pharm

    Los Angeles, California, 90033

  • Hem Onc Assoc of Northern NJ; Carol G. Simon Canc Ctr

    Morristown, New Jersey, 07962

  • Columbia University Medical Center

    New York, New York, 10032

  • INTEGRIS Cancer Inst of OK

    Oklahoma City, Oklahoma, 73142

  • Ventura County Hematology-Oncology Specialists

    Oxnard, California, 93030

  • Purchase Cancer Group

    Paducah, Kentucky, 42001

  • Wilshire Oncology Medical Group

    Pasadena, California, 91750

  • Kootenai Cancer Center

    Post Falls, Idaho, 83854

  • SW Virginia Hem Onc

    Roanoke, Virginia, 24014

  • Texas Cancer Center - Sherman

    Sherman, Texas, 75090-0504

  • Arizona Oncology

    Tucson, Arizona, 85704

  • Arizona Clinical Research Ctr

    Tucson, Arizona, 85715

  • Northwest Cancer Specialists - Vancouver

    Vancouver, Washington, 98684

  • Shenandoah Oncology Associates

    Winchester, Virginia, 22601

  • Yakima Valley Memorial Hospital/North Star Lodge

    Yakima, Washington, 98902

Other trials in United States

About this study

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

This open-label, multicenter, randomized study compared the efficacy, safety and pharmacokinetics of obinutuzumab (RO5072759; GA101) 1000 mg versus 2000 mg in participants with previously untreated CLL. Participants were randomized to receive a maximum of 8 cycles (28-day cycle) of obinutuzumab (1000 mg intravenous [IV] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of each subsequent cycle up to 8 cycles or maximum of 8 cycles of obinutuzumab (2000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of each subsequent cycle up to 8 cycles.

Being tested
Obinutuzumab, Corticosteroids
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ObinutuzumabDrug

    Also called RO5072759; GA101

    Participants were administered obinutuzumab either at 1000 mg or 2000 mg on Day 1, 8, 15 of Cycle 1 and then on Day 1 of each 21 day cycles for up to 8 cycles.

  • CorticosteroidsDrug

    Participants were administered corticosteroids IV prior to the initial dose.

Study groups in NCT01414205
Study groupRoleWhat they receive
Obinutuzumab 1000 mgExperimentalParticipants 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.
Receives: Drug: Obinutuzumab; Drug: Corticosteroids
Obinutuzumab 2000 mgExperimentalParticipants 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.
Receives: Drug: Obinutuzumab; Drug: Corticosteroids

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    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.

    Measured: Week 32

Secondary outcomes (14)

  1. Progression-free Survival (PFS)

    PFS was defined as the time from the randomization to the first occurrence of progression or death, whichever occurred first.

    Measured: Up to 4 years, 5 months

  2. Duration of Response

    Measured: Up to 4 years, 5 months

  3. Number of Participants Surviving at End-of-Study

    Measured: Up to 4 years, 5 months

  4. Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

    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.

    Measured: Up to 4 years, 5 months

  5. Percentage of Participants With Adverse Events of Interest

    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.

    Measured: Up to 4 years, 5 months

  6. Percentage of Participants With Adverse Events Leading to Study Discontinuation

    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.

    Measured: Up to 4 years, 5 months

  7. PK Parameter: Maximum Serum Concentration (Cmax)

    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).

    Measured: Day 148 (at end of infusion)

  8. PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt )

    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).

    Measured: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

  9. PK Parameter: Clearance at Steady State (CLss)

    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).

    Measured: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

  10. PK Parameter: Volume of Distribution at Steady State (Vss)

    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.

    Measured: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

  11. PK Parameter: Terminal Half-Life (t1/2)

    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.

    Measured: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

  12. PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits)

    Blood 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).

    Measured: Months 3, 6, 9, and 12

  13. Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion

    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.

    Measured: Up to 4 years, 5 months

  14. Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery

    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.

    Measured: Up to 4 years, 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2011 (estimated)
  2. Study start31 Oct 2011
  3. Primary completion31 Mar 2013
  4. Study completion31 Mar 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01414205
Sponsor's protocol ID
GAO4768g
Other IDs
GO25677
Status last verified
Mar 2017
First submitted
10 Aug 2011
Last updated
17 Apr 2017

Publications

  • Byrd JC, Flynn JM, Kipps TJ, Boxer M, Kolibaba KS, Carlile DJ, Fingerle-Rowson G, Tyson N, Hirata J, Sharman JP. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia. Blood. 2016 Jan 7;127(1):79-86. doi: 10.1182/blood-2015-03-634394. Epub 2015 Oct 15.

    PubMed 26472752

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Obinutuzumab and Corticosteroids in people with Lymphocytic Leukemia, Chronic, run by Genentech, Inc. at 31 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Week 32). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01414205, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2017.

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