BH39147

BH39147

A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination with Idasanutlin and Venetoclax in Patients with Relapsed or Refractory Follicular Lymphoma and Obinutuzumab or Rituximab in Combination with Idasanutlin and Venetoclax in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Disease:

Lymphoma -> follicular lymphoma (FL), diffuse large b-cell lymphoma (DLBCL)

Summary:

Follicular lymphoma (slow growing) and diffuse large b-cell lymphoma (fast growing) are forms of non-Hodgkin lymphoma, a cancer of the white blood cells. Symptoms include enlarged lymph nodes, high temperature, sweating at night, weight loss, low blood counts and enlarged organs in the abdomen.

This trial is for patients who have follicular lymphoma or diffuse large b-cell lymphoma which has returned after treatment. Patients will receive idasanutlin, venetoclax and either obinutuzumab or rituximab. Idasanutlin is a new drug taken by mouth, and works by ‘unleashing’ the body’s own powerful anti-cancer system against the lymphoma cells. Venetoclax is taken by mouth and primes lymphoma cells to undergo programmed cell death. Obinutuzumab and rituximab (a lymphoma targeting antibody) are given through an intravenous drip.

The aim of the trial is to see whether the combination of medications is effective and well tolerated in treating these forms of non-Hodgkin lymphoma.

Eligibility:

Include, but not limited to, the following:

Inclusion Criteria:
1. Eastern Cooperative Oncology Group (ECOG) of 0-2
2. B-cell lymphoma classified and defined as in Protocol
3. Histologically documented CD20-positive lymphoma
4. Fluorodeoxyglucose (FDG)-avid lymphoma (that is [i.e.], PET-positive lymphoma)
5. At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT or MRI
6. Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL

Exclusion Criteria:
1. Known CD20-negative status at relapse or progression
2. Prior allogeneic stem-cell transplantation (SCT)
3. Completion of autologous SCT within 100 days prior to Day 1 of Cycle 1
4. Prior standard or investigational anti-cancer therapy as specified in Protocol
5. Clinically significant toxicity (other than alopecia) from prior therapy as defined in Protocol
6. Grade 3b FL
7. History of transformation of indolent disease to DLBCL (expansion-phase only)
8. Central nervous system lymphoma or leptomeningeal infiltration
9. Treatment with systemic corticosteroids >20 mg/day, prednisone or equivalent
10. Clinical conditions requiring treatment with oral or parenteral anticoagulants or antiplatelet agents (unless treatment can be discontinued 7 days (or 5 half-lives) prior to initiation of study treatment)
11. History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies
12. Known hypersensitivity or allergy to murine products or any component of the obinutuzumab, rituximab, idasanutlin, or venetoclax formulation
13. Current or history of HEPATITIS as defined in protocol
14. History of progressive multifocal leukoencephalopathy (PML)
15. History of other malignancy that could affect compliance with the protocol or interpretation of results
16. Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results *NOTE: See Protocol for further information
17. Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, or anticipation of a major surgical procedure during the study
18. Inadequate hematologic function as defined in Protocol
19. Abnormal laboratory values as defined in Protocol
20. Life expectancy <3 months

Contact person:

Zelda Herbst
Email zherbst@linear.org.au
Phone 08 6382 5100


Email
Phone

Principal Investigator:

Dr Bradley Augustson

08 6457 7600

Sponsor:

F. Hoffmann-La Roche

Phase:

Ib/II

Protocol Number:

BH39147

Trial Registration Number:

NCT03135262

Clinical Trials.gov

ANZ Clinical Trial Registry