Tafasitamab with lenalidomide and rituximab for newly diagnosed follicular and marginal zone lymphoma

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

This trial will test whether adding tafasitamab to rituximab and lenalidomide is safe and helps people newly diagnosed with follicular lymphoma or marginal zone lymphoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 65 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Masonic Cancer Center, University of Minnesota (Academic / other)
• Drugs / interventions: tafasitamab, rituximab
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT06792825 on ClinicalTrials.gov

What this trial studies

This is a phase 2, Simon two-stage design testing tafasitamab added to rituximab and lenalidomide in two parallel, independent cohorts of treatment‑naïve follicular lymphoma (stage 1–3a, CD20+) and marginal zone lymphoma. Each cohort is evaluated separately for safety and anti-lymphoma activity with predefined early stopping rules in the first stage if results are inadequate. Participants receive the combination regimen and are followed for response, side effects, and duration of remission. Informed consent is obtained before any study treatment and procedures are performed at the coordinating site.

Who should consider this trial

Good fit: Ideal candidates are people with histologically confirmed CD20-positive follicular lymphoma (stage 1–3a) or marginal zone lymphoma who have not received prior systemic therapy and who meet treatment criteria such as bulky disease, B symptoms, or organ compromise.

Not a fit: Patients who have received prior systemic lymphoma therapy, whose disease does not require immediate treatment, or whose histology or stage falls outside the trial criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase response rates and lead to longer remissions while offering a chemo-sparing frontline option for these lymphomas.

How similar studies have performed: Rituximab plus lenalidomide (R2) has shown benefit in follicular and marginal zone lymphoma and tafasitamab plus lenalidomide is active in relapsed DLBCL, but combining all three agents in untreated FL/MZL is a novel approach.

Eligibility criteria

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.

Where this trial is running

Minneapolis, Minnesota

• Masonic Cancer Center — Minneapolis, Minnesota, United States (Recruiting)

Study contacts

• Study coordinator: Sanjal Desai, MD

Conditions Follicular Lymphoma; Marginal Zone Lymphoma