Clinical trial NCT00517530: A Dose-Escalating Study of Obinutuzumab in Patients With B-lymphocyte Antigen (CD20+) Malignant Disease (GAUGUIN)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-08-17
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study
timeFrame: Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)
measure: Percentage of Participants With Best Overall Response in Phase II of the Study
timeFrame: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
Secondary outcomes:
measure: Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study
timeFrame: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
measure: Percentage of Participants With Partial Response (PR) in Phase II of the Study
timeFrame: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)
measure: Progression-free Survival (PFS) in Phase II of the Study
timeFrame: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
measure: Duration of Response by Disease Type in Phase II of the Study
timeFrame: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
measure: Participants With Event-Free Survival (EFS) in Phase II of the Study
timeFrame: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)
measure: Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study
timeFrame: by the end of Phase II (within 3 years, 4 months)
measure: Percentage of Retreated Participants With Response
timeFrame: by Cutoff Date: 25 November 2013 (within 4 years, 2 months)
measure: Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants
timeFrame: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)
measure: Area Under the Concentration-time Curve of Obinutuzumab Administered on Day 1 of Cycle 1 in Phase I of the Study
timeFrame: Day 1 of Cycle 1
Other outcomes:
measure: Maximum Plasma Concentration (Cmax) of Obinutuzumab in CLL Patients
timeFrame: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)
Locations:
city: Creteil
country: France
city: Le Mans
country: France
city: Lille
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Paris
country: France
city: Paris
country: France
city: Pessac
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Rouen
country: France
city: Toulouse
country: France
city: Tours
country: France
city: Vandoeuvre Les Nancy
country: France
city: Köln
country: Germany
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.