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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00517530
First received: August 16, 2007
Last updated: August 19, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: Obinutuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Best Overall Response in Phase II of the Study [ Time Frame: by Cutoff Date: 31MAR2012 (within 3 years, 4 months) ] [ Designated as safety issue: No ]
    Best overall response (BOR) was defined as the percentage of participants with a complete response (CR) or partial response (PR)


Secondary Outcome Measures:
  • Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study [ Time Frame: by Cutoff Date: 31MAR2012 (within 3 years, 4 months) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Partial Response (PR) in Phase II of the Study [ Time Frame: by Cutoff Date: 31MAR2012 (within 3 years, 4 months) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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 PET-positive with histological confirmation.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Retreated Participants With Response [ Time Frame: by Cutoff Date: 25NOV2013 (within 4 years, 2 months) ] [ Designated as safety issue: No ]
    Patients who might benefit from retreatment were allowed to be treated again at the request of the investigator.


Enrollment: 134
Study Start Date: September 2007
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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.
  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: NCT00517530

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
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00517530     History of Changes
Other Study ID Numbers: BO20999 
Study First Received: August 16, 2007
Results First Received: July 14, 2015
Last Updated: August 19, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Obinutuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 26, 2016