HM2023-43:Ph 2 Trial of Tafasitamab With Lenalidomide+Rituximab in Treatment-naive FL and MZL

HM2023-43: A Phase 2 Trial of Tafasitamab in Combination With Lenalidomide+Rituximab in Treatment-naive Follicular Lymphoma and Marginal Zone Lymphoma

The study follows a Simon's two-stage phase II trial design to evaluate the safety and efficacy of tafasitamab added to rituximab and lenalidomide for two treatment-naïve, parallel, independent cohorts: follicular lymphoma (FL) and marginal zone lymphoma (MZ). Each cohort, FL and MZ, will be evaluated separately. This study is presented to the patient and consent is signed prior to the initiation of treatment for their primary malignancy.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Tafasitamab; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sanjal Desai, MD; Phone Number: 612-624-9452; Email: desai171@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Masonic Cancer Center
      • Contact: Sanjal Desai, MD; Phone Number: 612-624-9452; Email: desai171@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed marginal zone lymphoma
• Histologically confirmed CD20+ follicular lymphoma stage 1, 2 or 3a
• No prior systemic therapy for lymphoma
• Must be in need of treatment as evidenced by one or more of the following criteria:
• Bulky disease defined as:
• a nodal or extranodal (except spleen) mass >7cm in its greater diameter or,
• involvement of at least 3 nodal or extranodal sites (each with a diameter greater than >3 cm)
• Presence of at least one of the following B symptoms:
• fever (>38C) of unclear etiology
• night sweats
• weight loss greater than 10% within the prior 6 months
• Any other symptoms attributable to lymphomatous mass
• Endangerment of vital organ due to lymphomatous mass including but not limited to:
• Symptomatic or massive splenomegaly
• Compression syndrome (including but not limited to ureteral, orbital, gastrointestinal)
• Pleural, pericardial or ascitic effusion regardless of cell count
• Follicular lymphoma in leukemic phase (>5 X 109/L circulating cells)

OR:

• Follicular lymphoma graded high-risk by FLIPI2 score (see Appendix III)
• Adequate organ function within 14 days (28 days for pulmonary or cardiac) of study registration
• Participants who are of childbearing potential or have partners of child-bearing potential must agree to either total abstinence or use of both a highly effective (IUD, hormonal contraceptives, tubal ligation or vasectomy), and effective contraception (male or female condom, diaphragm or cervical cap) for the duration of treatment and for 12 months after the last dose of study drug.
• Able to tolerate prophylactic anticoagulation/antiplatelet therapy while on lenalidomide
• Able to provide written voluntary consent prior to the performance of any research related tests or procedures (or the subject's legally authorized representative (LAR) if enrollment of persons with diminished capacity is permitted - general permitted for Phase II and greater studies)

Exclusion Criteria:

• Seropositive for or active viral infection with hepatitis B virus (HBV):
• HBV surface antigen (HBsAg) positive
• HBV surface antigen (HBsAg) negative, HBV surface antibody (anti-HBs) positive and/or HBV core antibody (anti-HBc) positive, and detectable viral DNA
• Hepatitis C virus (HCV) positive subjects with chronic hepatitis C, or subjects with an active hepatitis C infection requiring anti-viral medication (at time of randomization).
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
• Prior history of lenalidomide use
• Prior history of malignancies, other than follicular or marginal zone lymphoma, unless the subject has been free of the disease for ≥ 5 years.
• Peripheral neuropathy ≥ grade 2 at time of screening
• Uncontrolled intercurrent illness.
• Active infection (requiring systemic therapy) or has received a live vaccine within 14 days prior to first dose of study drug.
• Presence or history of CNS involvement by lymphoma
• Patients who are not willing to take venous thromboembolic (VTE) prophylaxis or antiplatelet therapy
• Recent ( <1 year ) arterial thrombosis (any) or venous thrombosis ≥ grade 3 by CTCAE 5.0.
• Pregnant or breastfeeding as agents used in this study are Pregnancy Category X.

Women of childbearing potential must have two negative pregnancy tests (serum or urine) prior to their first dose of lenalidomide, and must agree to scheduled pregnancy testing while on treatment regardless of their birth control choice, per the requirements of the lenalidomide risk evaluation and mitigation strategy (REMS) program.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Follicular Lymphoma; On Cycle 1, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on Day 1, Day 8, Day 15 and Day 22, and lenalidomide 20 mg PO Day 1 through Day 21. On Cycles 2-3, patients will receive tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on day 1, and lenalidomide 20 mg PO Day 1-21. On Cycles 4-6, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Rituximab 375 mg/m2 IV on Day 1, and lenalidomide 20 mg PO from Day 1-21. At the end of Cycle 6, patients on both cohorts will be assessed by Lugano standard. Patients in complete remission (CR) will continue on tafasitamab/rituximab and discontinue lenalidomide. Patients with partial response (PR) or stable disease (SD) will continue on all three drugs, tafasitamab/rituximab/lenalidomide, and if progressive disease (PD) will discontinue study.	Drug: Rituximab; Rituximab 375 mg/m2 IV on day 1; Other Names: R2; Drug: Tafasitamab; Tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22.; Drug: Lenalidomide; Lenalidomide 20 mg PO Day 1 through Day 21
Experimental: Marginal Zone Lymphoma; On Cycle 1, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on Day 1, Day 8, Day 15 and Day 22, and lenalidomide 20 mg PO Day 1 through Day 21. On Cycles 2-3, patients will receive tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on day 1, and lenalidomide 20 mg PO Day 1-21. On Cycles 4-6, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Rituximab 375 mg/m2 IV on Day 1, and lenalidomide 20 mg PO from Day 1-21. At the end of Cycle 6, patients on both cohorts will be assessed by Lugano standard. Patients in complete remission (CR) will continue on tafasitamab/rituximab and discontinue lenalidomide. Patients with partial response (PR) or stable disease (SD) will continue on all three drugs, tafasitamab/rituximab/lenalidomide, and if progressive disease (PD) will discontinue study.	Drug: Rituximab; Rituximab 375 mg/m2 IV on day 1; Other Names: R2; Drug: Tafasitamab; Tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22.; Drug: Lenalidomide; Lenalidomide 20 mg PO Day 1 through Day 21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR)	Estimate complete response (CR) at the end of study (after 12 cycles around 1 year) regimen of tafasitamab with lenalidomide and rituximab.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR)	Estimate complete response (CR) rate after 6 cycles of treatment.	6 months
Overall response rate (ORR)	Estimate overall response rate (ORR) at the end of treatment (around 1 year).	1 year
Progression of disease (POD24)	Estimate progression of disease (POD24) within 24 months (2 years)	2 years
Progression free survival (PFS)	Estimate progression free survival (PFS) at 3 years after registration on study	3 years
Overall survival (OS)	Estimate overall survival (OS) at 3 years after registration on study	3 years
Rate of histologic conversion to DLBCL	Estimate rate of histologic conversion to DLBCL at any point on study.	3 years

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2025
• Primary Completion (Estimated): July 8, 2029
• Study Completion (Estimated): July 8, 2031

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Rituximab
• Other Study ID Numbers: 2023LS183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No