NCT00517530

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
134

participants targeted

Target at P75+ for phase_1 lymphoma

Timeline
Completed

Started Sep 2007

Typical duration for phase_1 lymphoma

Geographic Reach
2 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 16, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 17, 2007

Completed
15 days until next milestone

Study Start

First participant enrolled

September 1, 2007

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2013

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

September 22, 2015

Completed
Last Updated

October 11, 2016

Status Verified

August 1, 2016

Enrollment Period

6.2 years

First QC Date

August 16, 2007

Results QC Date

July 14, 2015

Last Update Submit

August 18, 2016

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study

    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

    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 Outcomes (9)

  • Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study

    by Cutoff Date: 31 March 2012 (within 3 years, 4 months)

  • Percentage of Participants With Partial Response (PR) in Phase II of the Study

    by Cutoff Date: 31 March 2012 (within 3 years, 4 months)

  • Progression-free Survival (PFS) in Phase II of the Study

    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

    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

    by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)

  • +4 more secondary outcomes

Other Outcomes (1)

  • Maximum Plasma Concentration (Cmax) of Obinutuzumab in CLL Patients

    at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)

Study Arms (8)

Phase I, NHL

EXPERIMENTAL

Participants in this NHL arm received multiple ascending doses between 50 and 2000 mg via intravenous infusion of obinutuzumab.

Drug: Obinutuzumab

Phase I, CLL

EXPERIMENTAL

Participants in this CLL arm received multiple ascending doses between 400 and 2000 mg via intravenous infusion of obinutuzumab.

Drug: Obinutuzumab

400/400 mg - Phase II, iNHL

EXPERIMENTAL

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

1600/800 mg - Phase II, iNHL

EXPERIMENTAL

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

400/400 mg - Phase II, aNHL

EXPERIMENTAL

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

1600/800 mg - Phase II, aNHL

EXPERIMENTAL

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

1000/1000 mg - Phase II, CLL

EXPERIMENTAL

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

Retreated Participants

EXPERIMENTAL

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

Interventions

ObinutuzumabDRUG

Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.

Also known as: RO5072759, GA101
1000/1000 mg - Phase II, CLL1600/800 mg - Phase II, aNHL1600/800 mg - Phase II, iNHL400/400 mg - Phase II, aNHL400/400 mg - Phase II, iNHLPhase I, CLLPhase I, NHLRetreated Participants

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Unknown Facility

Créteil, 94010, France

Location

Unknown Facility

Le Mans, 72015, France

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Marseille, 13273, France

Location

Unknown Facility

Montpellier, 34295, France

Location

Unknown Facility

Nantes, 44093, France

Location

Unknown Facility

Paris, 75475, France

Location

Unknown Facility

Paris, 75651, France

Location

Unknown Facility

Pessac, 33604, France

Location

Unknown Facility

Pierre-Bénite, 69495, France

Location

Unknown Facility

Rennes, 35033, France

Location

Unknown Facility

Rouen, 76038, France

Location

Unknown Facility

Toulouse, 31059, France

Location

Unknown Facility

Tours, 37044, France

Location

Unknown Facility

Vandœuvre-lès-Nancy, 54511, France

Location

Unknown Facility

Cologne, 50924, Germany

Location

Related Publications (6)

  • Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.

    PMID: 31050355DERIVED

  • Cartron G, Hourcade-Potelleret F, Morschhauser F, Salles G, Wenger M, Truppel-Hartmann A, Carlile DJ. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. Haematologica. 2016 Feb;101(2):226-34. doi: 10.3324/haematol.2015.133421. Epub 2015 Dec 11.

    PMID: 26659915DERIVED

  • Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. doi: 10.1182/blood-2014-07-586610. Epub 2014 Aug 20.

    PMID: 25143487DERIVED

  • Morschhauser FA, Cartron G, Thieblemont C, Solal-Celigny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. doi: 10.1200/JCO.2012.46.9585. Epub 2013 Jul 8.

    PMID: 23835718DERIVED

  • Salles GA, Morschhauser F, Solal-Celigny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. doi: 10.1200/JCO.2012.46.9718. Epub 2013 Jul 8.

    PMID: 23835715DERIVED

  • Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. doi: 10.1182/blood-2012-01-404368. Epub 2012 Mar 19.

    PMID: 22431570DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Limitations and Caveats

Pharmacodynamic results were limited because number of participants was inversely proportional to length of follow-up. In other words, there were fewer participants still in the trial as the follow-up period became longer.

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche
genentech@druginfo.com
800 821-8590

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 16, 2007

First Posted

August 17, 2007

Study Start

September 1, 2007

Primary Completion

November 1, 2013

Study Completion

November 1, 2013

Last Updated

October 11, 2016

Results First Posted

September 22, 2015

Record last verified: 2016-08

Locations

FR(15)DE(1)