A Safety and Pharmacokinetics Study of GDC-0199 (ABT-199) in Patients With Non-Hodgkin's Lymphoma
Conditions
Non-Hodgkin's Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, Non-Hodgkin
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: CHOP Type: Drug
Name: GDC-0199 Type: Drug
Name: obinutuzumab Type: Drug
Name: rituximab [MabThera/Rituxan] Type: Drug
Overall Status
Recruiting
Summary
This is a multicenter, open-label, dose-finding study of GDC-0199 administered orally in combination with MabThera/Rituxan (R) or obinutuzumab (G) and standard doses of cyclophosphamide, doxorubicin, vincristine and oral prednisone (CHOP) in patients with Non-Hodgkins Lymphoma (NHL). Patients will be randomized to one of two treatment arms of GDC-0199 in combination with R-CHOP and G-CHOP. The study will consist of two stages, a dose-finding stage and an expansion stage. The maximum tolerated dose (MTD) of GDC-0199 in combination with R-CHOP and G-CHOP will be determined during the dose-finding stage.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

General Inclusion Criteria:

- Patients, age > = 18 years

- At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its longest dimension

- Ability and willingness to comply with the study protocol procedures

- Confirmed availability of archival or freshly biopsied tumor tissue prior to study enrollment

- ECOG performance status of 0, 1 or 2

- Adequate hematologic function

- For female patients of childbearing potential, agreement to use highly effective forms of contraception

Dose Escalation Portion of the Study:

- Patients must have histologically confirmed B-cell non-Hodgkin's Lymphoma (NHL)

- Patients must have never received previous R-CHOP treatment

- Any relapsed/refractory patients that are enrolled during the dose escalation should have received only a single previous treatment regimen

Expansion Portion of the Study:

- Patients must have previously-untreated diffuse large, B-cell lymphoma

- International prognostic index (IP) score must be 2-5

Exclusion Criteria:

General Exclusion Criteria:

- Contraindication to receive any of the individual components of CHOP, rituximab or obinutuzumab

- Primary CNS lymphoma

- Vaccination with live vaccines within 28 days prior to randomization

- History of other malignancy that could affect compliance with the protocol or interpretation of results

- Evidence of significant, concomitant disease or illness

- Use of CYP3A inhibitors or inducers within 7 days of the first dose of GDC-0199

- Requires use of Warfarin

- Recent major surgery

- Women must not be pregnant or breastfeeding

Dose Escalation Portion of the Study:

- Prior anthracycline therapy

- Chemotherapy or other investigational therapy within 5 half-lives of a biologic agent with minimum of 28 days prior to the start of Cycle 1

- Histologically confirmed mantle cell lymphoma (MCL) or small lymphocytic lymphoma (SLL)

Expansion Portion of the Study:

- Patients with transformed lymphoma

- Prior therapy for non-Hodgkins Lymphoma (NHL)

- Current Grade > 1 peripheral neuropathy

- Ongoing therapy with calcium channel entry blocker drugs or therapy within 30 days of C1D1

- Prior radiotherapy to the mediastinal/pericardial region
Locations
Huntsville, Alabama, United States
Status: Not yet recruiting
Fullerton, California, United States
Status: Not yet recruiting
Greenbrae, California, United States
Status: Not yet recruiting
Los Angeles, California, United States
Status: Not yet recruiting
Northridge, California, United States
Status: Not yet recruiting
Redondo Beach, California, United States
Status: Not yet recruiting
San Luis Obispo, California, United States
Status: Not yet recruiting
Denver, Colorado, United States
Status: Not yet recruiting
Hollywood, Florida, United States
Status: Not yet recruiting
St. Louis, Missouri, United States
Status: Not yet recruiting
Hackensack, New Jersey, United States
Status: Recruiting
Farmington, New Mexico, United States
Status: Not yet recruiting
New York, New York, United States
Status: Recruiting
Rochester, New York, United States
Status: Recruiting
Hamilton, Ohio, United States
Status: Not yet recruiting
Middletown, Ohio, United States
Status: Not yet recruiting
Philadelphia, Pennsylvania, United States
Status: Recruiting
Nashville, Tennessee, United States
Status: Not yet recruiting
Concord, New South Wales, Australia
Status: Not yet recruiting
Woolloongabba, Queensland, Australia
Status: Not yet recruiting
East Melbourne, Victoria, Australia
Status: Recruiting
Parkville, Victoria, Australia
Status: Recruiting
Edmonton, Alberta, Canada
Status: Not yet recruiting
Kelowna, British Columbia, Canada
Status: Not yet recruiting
Vancouver, British Columbia, Canada
Status: Recruiting
Montréal, Quebec, Canada
Status: Not yet recruiting
Quebec, Canada
Status: Not yet recruiting
Brno, Czech Republic
Status: Not yet recruiting
Hradec Kralove, Czech Republic
Status: Not yet recruiting
Ostrava - Poruba, Czech Republic
Status: Not yet recruiting
Praha 2, Czech Republic
Status: Not yet recruiting
Creteil, France
Status: Recruiting
La Roche sur Yon, France
Status: Not yet recruiting
Le Mans Cedex 02, France
Status: Not yet recruiting
Lille, France
Status: Recruiting
Montpellier, France
Status: Recruiting
Nantes, France
Status: Recruiting
Nimes, France
Status: Not yet recruiting
Paris, France
Status: Not yet recruiting
Pierre-Benite, France
Status: Recruiting
Rennes cedex 09, France
Status: Not yet recruiting
Rouen, France
Status: Recruiting
Tours, France
Status: Not yet recruiting
Vandoeuvre-les-nancy, France
Status: Not yet recruiting
Budapest, Hungary
Status: Not yet recruiting
Debrecen, Hungary
Status: Not yet recruiting
Napoli, Campania, Italy
Status: Not yet recruiting
Roma, Lazio, Italy
Status: Not yet recruiting
Genova, Liguria, Italy
Status: Not yet recruiting
Palermo, Sicilia, Italy
Status: Not yet recruiting
Pisa, Toscana, Italy
Status: Not yet recruiting
Amsterdam, Netherlands
Status: Recruiting
Rotterdam, Netherlands
Status: Recruiting
Utrecht, Netherlands
Status: Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain
Status: Not yet recruiting
Barcelona, Spain
Status: Not yet recruiting
Barcelona, Spain
Status: Not yet recruiting
Madrid, Spain
Status: Not yet recruiting
Madrid, Spain
Status: Not yet recruiting
Salamanca, Spain
Status: Not yet recruiting
Start Date
June 2014
Completion Date
April 2018
Sponsors
Hoffmann-La Roche
Source
Hoffmann-La Roche
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page