A Safety and Pharmacokinetics Study of GDC-0199 (ABT-199) in Patients With Non-Hodgkin's Lymphoma

Phase 1

• Conditions: B-cell non-hodgkin's lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL); MedDRA version: 20.0 Level: PT Classification code 10012821 Term: Diffuse large B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10029601 Term: Non-Hodgkin's lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10029600 Term: Non-Hodgkin's lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003749-40-CZ
• Lead Sponsor: F. Hoffmann- La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-11-21
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 264

Inclusion Criteria

General Inclusion Criteria:
- Patients, age >= 18 years
- At least one bi-dimensionally measurable lymphoma lesion defined as > 1.5 cm in its longest dimension which is also FDG avid by screening PET scan
- 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 and male patients with female partners of childbearing potential, agreement to use highly effective forms of contraception

Dose Finding Portion of the Study:
- Patients must have histologically confirmed B-cell non-Hodgin'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

Phase II Portion of the Study:
- Patients must have previously-untreated CD20-positive diffuse large, B-cell lymphoma
- International prognostic index (IPI) score must be 2-5
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

General Exclusion Criteria:
- Contraindication to receive any of the individual components of CHOP, rituximab or obinutuzumab
- CNS lymphoma or primary mediastinal DLBCL
- 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 venetoclax
- Recent major surgery
- Women must not be pregnant or breastfeeding

Dose Finding Portion of the Study:
- Histologically confirmed mantle cell lymphoma (MCL) or small lymphocytic lymphoma (SLL)

Phase II Portion of the Study:
- Patients with transformed lymphoma (patients with discordant bone marrow involvement [i.e., low grade histology in bone marrow] may be considered after discussion with the Medical Monitor)
- Prior therapy for non-hodgkin's lymphoma (NHL)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified