Tazemetostat in Combination With Zanubrutinib and Anti-CD20 Monoclonal Antibody in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT06824701 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI183680
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to learn if the study drug Tazemetostat combined with Zanubrutinib and anti-CD20 monoclonal antibody is safe and effective in treating patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma.

Conditions

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of tazemetostat in combination with zanubrutinib and anti-CD20 mAb

  To determine the MTD of tazemetostat in with zanubrutinib and anti-CD20 mAb. MTD is the highest dose where 0 of the first 3 or 1 of 6 patients had a dose-limiting Toxicity (DLT) during Cycle 1 of tazemetostat treatment. This will report the number of patients with DLTs at Dose Level (DL)-1, DL1, and DL2. A DLT is: A Grade ≥ 3 non-hematologic toxicity lasting \>3 days EXCEPT: * Alopecia * Grade 3 fatigue, asthenia, anorexia, constipation, nausea, vomiting, or diarrhea not requiring tube feeding, total parenteral nutrition, or hospitalization * Grade 3 or 4 tumor lysis syndrome (resolved ≥7 days) or electrolyte abnormalities (resolved to \< Grade 2 in \<72 hours) * Grade 3 alkaline phosphatase, gamma-glutamyl transferase, amylase, or lipase elevation \< 72 hours. Any of these hematologic toxicities: * Grade 4 neutropenia, febrile neutropenia, or thrombocytopenia * Grade 5 hematologic toxicity Dose delay due to toxicity \> 28 days

  2 years

Secondary Outcomes (7)

• Overall response rate (ORR) rate at Cycle 7 Day 1 (C7D1)

  8 months

• Very Good Partial Response (VGPR) Rate at Cycle 7 Day 1 (C7D1)

  8 months

• Median Duration of Response (DOR)

  7 years

• Median Progression-Free Survival (PFS)

  2 years

• Progression-Free Survival (PFS) at two years after treatment initiation.

  2 years

Study Arms (1)

Treatment: All Patients

EXPERIMENTAL

The study will investigate the effectiveness of Tazemetostat in combination with Zanubrutinib and anti-CD20 monoclonal antibody

Drug: Tazemetostat; Drug: Zanubrutinib; Drug: Rituximab; Drug: Obinutuzumab

Interventions

Tazemetostat DRUG

Tazemetostat will be self-administered BID as an oral treatment on a 28-day cycle.

Also known as: Tazverik

Treatment: All Patients

Zanubrutinib DRUG

Zanubrutinib will be self-administered BID as an oral treatment on a 28-day cycle.

Also known as: Brukinsa

Treatment: All Patients

Rituximab DRUG

Rituximab or a biosimilar will be administered intravenously per standard of care.

Also known as: Ruxience, Rituxan

Treatment: All Patients

Obinutuzumab DRUG

Obinutuzumab will be administered intravenously on days 1, 8, 15 of cycle 1 and then day 1 of cycles 2 to 12.

Also known as: Gazyva

Treatment: All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject aged ≥ 18 years.
• Eligible histologies include MCL, MZL (including splenic, nodal, and extranodal sub-types), and WM who received at least one line of prior systemic therapy and FL who received at least two prior lines of systemic therapy
• Measurable disease: at least one lesion \>1.5 cm in longest diameter or 1 extranodal lesion \>1 cm in the longest diameter.
• Note: For MZL, isolated splenomegaly and involvement of any biopsy proven extranodal site is considered measurable for this study. For MCL, clonal lymphocyte measured by flow cytometry is considered measurable. For WM, serum IgM level \>0.5 g/dL is considered measurable.
• Patients must have an indication for treatment.
• For R/R FL: active disease requiring treatment
• For R/R MCL: active disease requiring treatment
• For R/R MZL: active disease requiring treatment
• For R/R WM: Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenstrom's Macroglobulinemia68
• Recurrent fever, night sweats, weight loss, fatigue
• Hyperviscosity
• Lymphadenopathy which is either symptomatic or bulky (≥ 5 cm in maximum diameter)
• Symptomatic hepatomegaly and/or splenomegaly
• Symptomatic organomegaly and/or organ or tissue infiltration
• Peripheral neuropathy due to WM

You may not qualify if:

• Prior exposure to tazemetostat or other inhibitor(s) of EZH2
• Any prior history of myeloid malignancies including MDS/AML or MPN
• Any prior history of T-LBL, T-ALL, or B-ALL
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drugs
• Major surgery within 4 weeks prior to enrollment
• Known history of bleeding diathesis or active bleeding
• Known history of stroke or intracranial hemorrhage within 6 months of enrollment
• Significant cardiovascular disease defined as:
• unstable angina or acute coronary syndrome within the past 2 months prior to study enrollment
• history of myocardial infarction within 3 months prior to study enrollment or documented LVEF by any method of ≤ 40% in the 12 months prior to study enrollment --≥ Grade 3 NYHA functional classification system of heart failure, uncontrolled or symptomatic arrhythmias
• Significant liver disease (\>Child Pugh Class A)
• Patients with CNS involvement
• Prolongation of the QT interval corrected for heart rate (QTcF) \> 480 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33).
• Correction of suspected drug induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
• Correction for underlying bundle branch block (BBB) allowed. ---Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker

Sponsors & Collaborators

• University of Utah: lead
• Ipsen: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Uta

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Interventions

tazemetostat; zanubrutinib; Rituximab; obinutuzumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Narendranath Epperla, MD, MS, FACP

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Kingsford

CONTACT

801-585-0115; rachel.kingsford@hci.utah.edu

Narendranath Epperla, MD, MS, FACP

CONTACT

801-585-0255; naren.epperla@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: February 13, 2025
• Study Start: September 12, 2025
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2033
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)