NCT04850495

Zanubrutinib in Combination With R-PolaCHP (ZaR-PolaCHP) for Newly Diagnosed Diffuse Large B-Cell Lymphoma

A Phase Ib Trial of Zanubrutinib in Combination With R-PolaCHP (ZaR-PolaCHP) for Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Yazeed Sawalha · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial seeks to find out the best dose and possible side effects and/or benefits of zanubrutinib in combination with the R-PolaCHP in treating patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Zanubrutinib is designed to block a protein called Bruton Tyrosine Kinase in order to stop cancer growth. R-CHOP is the acronym for the combination of five drugs: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. It is the most widely used chemoimmunotherapy regimen for DLBCL and is considered the standard-of-care treatment for patients with DLBCL. Three of the drugs in R-CHOP (cyclophosphamide, doxorubicin and vincristine) are chemotherapy drugs. Rituximab is a type of immunotherapy and prednisone is a type of steroids.

Detailed description

PRIMARY OBJECTIVE: I. Determine the safety, toxicity profile and recommended phase 2 dose (RP2D) of zanubrutinib in combination with ZaR-PolaCHP (ZaR-PolaCHP) for patients with previously untreated diffuse large B-cell lymphoma (DLBCL). SECONDARY OBJECTIVES: I. Determine the objective response rate (ORR) (complete and partial responses), progression-free survival (PFS) and overall survival (OS) of ZaR-CHOP in patients treated at the RP2D. II. Provide descriptive data on treatment exposure to zanubrutinib and R-CHOP including treatment discontinuation rate and relative dose intensity. EXPLORATORY OBJECTIVES: I. Examine archival tumor samples attained before starting treatment on trial to determine the clinical outcomes of molecularly defined DLBCL subtypes in patients treated with ZaR-Pola-CHP or ZaR-CHOP. II. Measure circulating tumor deoxyribonucleic acid (DNA) (ctDNA) to correlate its presence with response by positron emission tomography (PET) imaging. OUTLINE: This is a dose de-escalation study of zanubrutinib and fixed-dose R-CHOP regimen followed by a dose-expansion study. Patients receive zanubrutinib orally (PO) once or twice daily on days 1-21, rituximab intravenously (IV) on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for 2 years.

Conditions

• Diffuse Large B-Cell Lymphoma
• Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
• Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Prednisone	Given PO
BIOLOGICAL	Rituximab	Given IV
DRUG	Vincristine Sulfate	Given IV
DRUG	Zanubrutinib	Given PO

Timeline

• Start date: 2021-11-16
• Primary completion: 2026-05-15
• Completion: 2026-06-15
• First posted: 2021-04-20
• Last updated: 2026-02-06

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study