A Dose-Escalating Study of Obinutuzumab in Patients With B-lymphocyte Antigen (CD20+) Malignant Disease (GAUGUIN)

August 18, 2016 updated by: Hoffmann-La Roche

An Open-label, Multicentre, Nonrandomized, Dose-escalating Phase I/II Study, With a Randomized Phase II Part, to Investigate the Safety and Tolerability of RO5072759 Given as Monotherapy in Patients With CD20+ Malignant Disease.

The primary objective for the phase I part of the study is to investigate the safety and tolerability of escalating intravenous (IV) doses of obinutuzumab given as monotherapy in participants with CD20+ (tumor-infiltrating lymphocytic) Malignant Disease, including B-cell chronic lymphocytic leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL). The primary objective for the phase II part of the study is to investigate the efficacy and safety of one dose of obinutuzumab in participants with relapsed/refractory CLL and NHL that is, in turn, either indolent (iNHL) or aggressive (aNHL).

It is an open label dose escalating study in phase I and open label in phase II, but the two doses in iNHL & aNHL are randomized (to high or low dose of the same open label treatment). CLL was not randomized as only one dose level was used.

Participants with a response who might gain additional benefit from being treated again in the opinion of the investigator may be enrolled in a Retreatment Period.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
134

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Creteil, France, 94010
      • Le Mans, France, 72015
      • Lille, France, 59037
      • Marseille, France, 13273
      • Montpellier, France, 34295
      • Nantes, France, 44093
      • Paris, France, 75651
      • Paris, France, 75475
      • Pessac, France, 33604
      • Pierre Benite, France, 69495
      • Rennes, France, 35033
      • Rouen, France, 76038
      • Toulouse, France, 31059
      • Tours, France, 37044
      • Vandoeuvre Les Nancy, France, 54511
  • Germany
      • Köln, Germany, 50924

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients, >=18 years of age;
  • Phase 1 only: CD20+ malignant disease (B-cell lymphoma or B-CLL);
  • Phase 2 only: relapsed or refractory indolent NHL, relapsed or refractory aggressive NHL or relapsed or refractory B-CLL
  • Have a clinical indication for treatment as determined by the investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Life expectancy >12 weeks

Exclusion Criteria:

  • Prior use of any investigational antibody therapy or other agent within 6 months of study start;
  • Prior use of any anti-cancer vaccine;
  • Prior use of standard anti-lymphoma/leukemia therapy or radiation therapy within 4 weeks of enrollment;
  • Prior use of MabThera (rituximab) within 8 weeks of study entry;
  • Prior administration of radioimmunotherapy 3 months prior to study entry;
  • Central nervous system (CNS) lymphoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase I, NHL
Participants in this NHL arm received multiple ascending doses between 50 and 2000 mg via intravenous infusion of obinutuzumab.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: Phase I, CLL
Participants in this CLL arm received multiple ascending doses between 400 and 2000 mg via intravenous infusion of obinutuzumab.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: 400/400 mg - Phase II, iNHL
Participants in this iNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: 1600/800 mg - Phase II, iNHL
Participants in this iNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: 400/400 mg - Phase II, aNHL
Participants in this aNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: 1600/800 mg - Phase II, aNHL
Participants in this aNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: 1000/1000 mg - Phase II, CLL
Participants in this CLL arm received an intravenous infusion of obinutuzumab 1000 mg on Days 1, 8, and 15 of Cycle 1 and obinutuzumab 1000 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 10 infusions. Each cycle was 21 days.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101
Experimental: Retreated Participants
Participants who might benefit from retreatment who were allowed to be treated again via intravenous infusion of obinutuzumab at the request of the investigator.
Drug: Obinutuzumab
Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.
Other Names:
  • RO5072759
  • GA101

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study
Time Frame: Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)
Dose-limiting toxicities were defined as obinutuzumab-related adverse events occurring within the first 28 days of each administration of obinutuzumab, with the exception of B-cell depletion and lymphopenia which are expected outcomes of treatment with obinutuzumab.
Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)
Percentage of Participants With Best Overall Response in Phase II of the Study
Time Frame: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
Best overall response (BOR) was defined as the percentage of participants with a complete response (CR) or partial response (PR)
by Cutoff Date: 31 March 2012 (within 3 years, 4 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study
Time Frame: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
A complete response was defined as the disappearance of all evidence of disease (NHL) and symptoms; normalization of biochemical abnormalities (NHL); regression of lymph nodes and nodal masses to normal size; decrease of nodes in the sum of the products of the greatest diameters (SPD); regression in size of the spleen and/or liver, should not be palpable, and disappearance of nodules related to lymphoma (CLL). Complete/unconfirmed (CRu) response includes NHL patients with one or more of the following: 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the SPD; 2) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). Complete Response with Incomplete Bone Marrow Recovery (CRi) was measured only in patients with CLL.
by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
Percentage of Participants With Partial Response (PR) in Phase II of the Study
Time Frame: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
A PR was defined as a >=50% decrease in SPD of the 6 largest nodes or nodal masses; no increase in size of other nodes, liver, or spleen; regression of splenic and hepatic nodules by >=50% in their SPD or, for single nodules, in the long axis (CLL only); and no new disease sites.
by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
Progression-free Survival (PFS) in Phase II of the Study
Time Frame: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
PFS was defined as the time from start of treatment to disease progression (PD) or death due to any cause, whichever occurred first. For non-Hodgkin's lymphoma participants, PD was defined as >= 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for participants with a partial response or non-responders or the appearance of any new lesion during or at the end of therapy. For chronic lymphocytic leukemia participants, PD was defined as: (1) A >= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules); a lymph node with a short axis of < 1.0 cm must increase by >= 50% and to a size of 1.5×1.5 cm or > 1.5 cm in the longest axis. (2) Appearance of any new lesion > 1 cm in the short axis. (4) A new site that is positron emission tomography (PET)-positive with histological confirmation.
by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
Duration of Response by Disease Type in Phase II of the Study
Time Frame: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
Duration of complete response was defined as the time from the first complete or partial response until disease progression (PD) or death, whichever occurred first. For non-Hodgkin's lymphoma participants, PD was defined as >= 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for participants with a partial response or non-responders or the appearance of any new lesion during or at the end of therapy. For chronic lymphocytic leukemia participants, PD was defined as: (1) A >= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules); a lymph node with a short axis of < 1.0 cm must increase by >= 50% and to a size of 1.5×1.5 cm or > 1.5 cm in the longest axis. (2) Appearance of any new lesion > 1 cm in the short axis. (4) A new site that is PET-positive with histological confirmation.
by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
Participants With Event-Free Survival (EFS) in Phase II of the Study
Time Frame: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
EFS is defined as the time from start of treatment to disease progression/relapse, death or, in case of early withdrawal from the treatment period, the (end) date of last dose, whatever comes first.
by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
Time Frame: by the end of Phase II (within 3 years, 4 months)
B-cell depletion was defined in two ways: definition 1 - decrease below 5% baseline level and definition 2 - decrease below 0.04 x 109/L. B-cell recovery was defined in two ways: definition 1 - return to at least 50% of baseline level and definition 2 - return to at least 0.08 x 109/L.
by the end of Phase II (within 3 years, 4 months)
Percentage of Retreated Participants With Response
Time Frame: by Cutoff Date: 25 November 2013 (within 4 years, 2 months)
Patients who might benefit from retreatment were allowed to be treated again at the request of the investigator.
by Cutoff Date: 25 November 2013 (within 4 years, 2 months)
Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants
Time Frame: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)
Obinutuzumab serum pharmacokinetic (PK) parameters in NHL participants following ascending doses.
at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)
Area Under the Concentration-time Curve of Obinutuzumab Administered on Day 1 of Cycle 1 in Phase I of the Study
Time Frame: Day 1 of Cycle 1
Blood samples were taken on Day 1 (pre-infusion, end of infusion, 3-6 hours post-infusion) of Cycle 1. Nonlinear mixed-effects modeling (with NONMEM software) was used to analyze the pooled samples for dose-concentration-time data of obinutuzumab.
Day 1 of Cycle 1

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Maximum Plasma Concentration (Cmax) of Obinutuzumab in CLL Patients
Time Frame: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)
at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 16, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 17, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 11, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BO20999
  • 2007-001103-37 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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