NCT05890352

Randomized Phase II Study of the Addition of Targeted Therapeutic Agents to Tafasitamab-Based Therapy in Non-Transplant-Eligible Patients With Relapsed/Refractory Large B-Cell Lymphoma

Recruiting now Phase 2 Last updated 16 October 2025

What this trial tests

Phase 2 trial testing Biospecimen Collection in Grade 3b Follicular Lymphoma in 227 participants. Currently enrolling.

Timeline

26 September 2023

Primary endpoint
31 December 2026

1 January 2029

Quick facts

Lead sponsor	SWOG Cancer Research Network
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	227
Start date	26 September 2023
Primary completion	31 December 2026
Estimated completion	1 January 2029
Sites	104 locations across United States

Drugs / interventions tested

• Biospecimen Collection
• Computed Tomography
• Lenalidomide — full drug profile →
• Magnetic Resonance Imaging
• Positron Emission Tomography
• Quality-of-Life Assessment
• Questionnaire Administration
• Tafasitamab — full drug profile →
• Tazemetostat (tazemetostat) — full drug profile →
• Zanubrutinib (ZANUBRUTINIB) — full drug profile →

Conditions studied

• Grade 3b Follicular Lymphoma — all drugs for Grade 3b Follicular Lymphoma →
• High Grade B-Cell Lymphoma — all drugs for High Grade B-Cell Lymphoma →
• High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements — all drugs for High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements →
• Recurrent Diffuse Large B-Cell Lymphoma — all drugs for Recurrent Diffuse Large B-Cell Lymphoma →

Sponsor

SWOG Cancer Research Network

Who can join

18 and older, any sex, with Grade 3b Follicular Lymphoma or High Grade B-Cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Progression-free survival (PFS)
  Time frame: From date of randomization to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 3 years
  Will be compared between participants randomized to control Arm 2 (tafasitamab + lenalidomide) versus (vs) experimental Arm 1 (tafasitamab + lenalidomide + tazemetostat), AND control Arm 2 vs experimental Arm 3 (tafasitamab + lenalidomide + zanubrutinib), respectively.
• Trial Outcome Index (TOI) score from the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) (Patient Reported Outcome [PRO] Study)
  Time frame: Baseline up to 3 months after randomization
  Will compare the trial outcome index (TOI) score between each experimental arm (Arm 1 and Arm 3) to the control arm (Arm 2). The TOI score is composed of the Physical Well-Being, Functional Well-Being, and lymphoma-specific subscale scores. The scores range from 0-116, with higher scores indicating a higher quality of life.

Sponsor's own description

This phase 2 trial studies the side effects and best dose of tazemetostat and zanubrutinib in combination with tafasitamab and lenalidomide, and to see how well these combinations work in treating patients with large B-cell lymphoma that returned or did not respond to earlier treatment. Tazemetostat is in a class of medications called EZH2 inhibitors. It helps to stop the spread of cancer cells. Zanubrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. The addition of tazemetostat or zanubrutinib to tafasitamab and lenalidomide may be able to shrink the cancer or extend the time without cancer symptoms coming back.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Therapeutic landscape of primary refractory and relapsed diffuse large B-cell lymphoma: Recent advances and emerging therapies.
   Bock AM, Epperla N. · · 2025 · cited 8× · PMID 40597378 · DOI 10.1186/s13045-025-01702-5
2. Exploring oncogenic roles and clinical significance of EZH2: focus on non-canonical activities.
   Wozniak M, Czyz M. · · 2025 · cited 2× · PMID 39776536 · DOI 10.1177/17588359241306026
3. Overcoming barriers to drug development and enrollment in clinical trials for adolescents and young adults with lymphoma.
   Toner K, Allen CE, Jain S, Kahl B, et al · · 2023 · cited 2× · PMID 38024612 · DOI 10.1002/jha2.787