Tafasitamab + Lenalidomide for CNS Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by James Rubenstein, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: James Rubenstein

Must not be taking: Anti-CD19 therapy

Disqualifiers: HIV, CNS PTLD, uncontrolled infection, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a combination of lenalidomide and Tafasitamab in patients with brain cancer that has returned after previous treatments. Lenalidomide, a derivative of thalidomide, is known to boost the immune system and directly target cancer cells, potentially improving drug delivery to the brain.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received systemic anti-cancer therapies within 2 weeks, radiation within 1 week, or antibody therapy within 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Tafasitamab and Lenalidomide for treating CNS Lymphoma?

Tafasitamab combined with Lenalidomide has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with studies indicating improved survival outcomes compared to other treatments. In particular, the combination demonstrated a significant overall survival benefit and durable responses in patients who were not eligible for stem cell transplants. ^{1 2 3 4 5}

What safety data exists for Tafasitamab and Lenalidomide treatment?

Tafasitamab and Lenalidomide have been studied together for treating certain types of lymphoma, and common side effects include infections, blood disorders, and digestive issues. These side effects were generally manageable, and no new safety concerns were found in long-term studies. Lenalidomide, a related drug, has reduced nerve and blood clot side effects compared to its predecessor, thalidomide. ^{1 2 5 6 7}

How is the drug combination of Tafasitamab and Lenalidomide unique for treating CNS Lymphoma?

The combination of Tafasitamab and Lenalidomide is unique because Tafasitamab is an anti-CD19 monoclonal antibody that enhances the immune system's ability to target cancer cells, and when combined with Lenalidomide, it has shown long-term clinical benefits and durable responses in similar conditions like diffuse large B-cell lymphoma (DLBCL). This combination is particularly beneficial for patients who are not eligible for stem cell transplants. ^{1 2 4 5 8}

Eligibility Criteria

Adults with relapsed B-cell CNS lymphoma, including those who've had stem cell transplants but not recent anti-cancer treatments or certain other therapies. Must have good organ function and no serious medical issues that could affect safety. Women of childbearing age must agree to pregnancy testing and use contraception.

Inclusion Criteria

I have another cancer, but it won't affect this trial's treatment.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I have CNS lymphoma in the brain and have undergone at least one treatment.

Exclusion Criteria

I am not pregnant or breastfeeding, and if of child-bearing potential, I am using effective birth control.

I have never received anti-CD19 or CAR-T therapy.

I haven't had cancer treatments like chemotherapy, radiation, or antibody therapy in the specified time before starting this trial.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive Tafasitamab and Lenalidomide to determine the maximum tolerated dose and recommended phase 2 dose

Up to 1 cycle (28 days)

Multiple visits for dosing and monitoring

Phase 2 Treatment

Participants receive Tafasitamab and Lenalidomide at the recommended phase 2 dose to evaluate clinical benefit

Up to 3 months

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Regular follow-up visits

Treatment Details

Interventions

• Lenalidomide (Immunomodulatory imide drugs (IMiDs))
• Tafasitamab (Monoclonal Antibodies)

Trial Overview The trial is exploring the effectiveness of Tafasitamab combined with Lenalidomide in patients with relapsed CNS lymphoma. It's an open-label study, meaning everyone knows what treatment they're getting, focusing on how well this combination crosses the blood-brain barrier.

Participant Groups

Group I: Phase 2 (Tafasitamab, Lenalidomide) Experimental Treatment 2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle at the recommended phase 2 dose.

Group II: Phase 1 (Tafasitamab, Lenalidomide) Experimental Treatment 2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle.

Lenalidomide is already approved in European Union, United States for the following indications:

🇪🇺 Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

🇺🇸 Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California, San Francisco San Francisco, CA

Who Is Running the Clinical Trial?

James Rubenstein Lead Sponsor

Incyte Corporation Industry Sponsor

References

1. Germany pubmed.ncbi.nlm.nih.gov

RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma. [2023] RE-MIND2 (NCT04697160) compared patient outcomes from the L-MIND (NCT02399085) trial of tafasitamab+lenalidomide with those of patients treated with other therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are autologous stem cell transplant ineligible. We present outcomes data for three pre-specified treatments not assessed in the primary analysis. Data were retrospectively collected from sites in North America, Europe, and the Asia Pacific region. Patients were aged ≥18 years with histologically confirmed DLBCL and received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients enrolled in the observational and L-MIND cohorts were matched using propensity score-based 1:1 nearest-neighbor matching, balanced for six covariates. Tafasitamab+lenalidomide was compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR), rituximab+lenalidomide (R2), and CD19-chimeric antigen receptor T-cell (CAR-T) therapies. The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and progression-free survival. From 200 sites, 3,454 patients were enrolled in the observational cohort. Strictly matched patient pairs consisted of tafasitamab+lenalidomide versus pola-BR (n = 24 pairs), versus R2 (n = 33 pairs), and versus CAR-T therapies (n = 37 pairs). A significant OS benefit was observed with tafasitamab+lenalidomide versus pola-BR (HR: 0.441; p = 0.034) and R2 (HR: 0.435; p = 0.012). Comparable OS was observed in tafasitamab+lenalidomide and CAR-T cohorts (HR: 0.953, p = 0.892). Tafasitamab+lenalidomide appeared to improve survival outcomes versus pola-BR and R2, and comparable outcomes were observed versus CAR-T. Although based on limited patient numbers, these data may help to contextualize emerging therapies for R/R DLBCL. CLINICAL TRIAL REGISTRATION: NCT04697160 (January 6, 2021).

2. Italy pubmed.ncbi.nlm.nih.gov

Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety in the phase II L-MIND study. [2023] Tafasitamab, an anti-CD19 immunotherapy, is used with lenalidomide for patients with autologous stem cell transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) based on the results of the phase II L-MIND study (NCT02399085). We report the final 5-year analysis. Eighty patients (≥18 years, 1-3 prior systemic therapies, ECOG PS 0-2) received co-administered tafasitamab and lenalidomide for up to 12 cycles, followed by tafasitamab monotherapy until disease progression (PD) or unacceptable toxicity. Primary endpoint was best objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses evaluated efficacy endpoints by prior lines of therapy (pLoT). At data cut-off on November 14, 2022, ORR was 57.5%, with complete response (CR) of 41.3% (n=33), which was consistent with prior analyses. With median follow-up (mFU) of 44.0 months, median DoR was not reached. Median PFS was 11.6 months [95% CI, 5.7-45.7] (mFU 45.6), and median OS was 33.5 months [95% CI, 18.3-NR] (mFU 65.6). Patients with 1 pLoT (n=40) showed higher ORR (67.5%; 52.5% CR) compared with patients with ≥2 pLoT (n=40; 47.5%; 30% CR), but median DoR was not reached in either subgroup. Other exploratory analyses revealed consistent long-term efficacy results across subgroups. Adverse events were consistent with previous reports and manageable, and their frequency decreased during tafasitamab monotherapy, with no new safety concerns. This final 5-year analysis of L-MIND demonstrates that this immunotherapy combination is well tolerated and has long-term clinical benefit with durable responses.

3. United States pubmed.ncbi.nlm.nih.gov

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. [2023] Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination.

4. United States pubmed.ncbi.nlm.nih.gov

Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison. [2022] Tafasitamab plus lenalidomide (TAFA + LEN) received accelerated US Food and Drug Administration approval and conditional European Medicines Agency approval for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for autologous stem cell transplant. This study investigates the relative efficacy of TAFA + LEN versus comparator treatments.

5. New Zealand pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. [2022] Tafasitamab (tafasitamab-cxix; MONJUVI®) is an Fc-modified (i.e. two amino acid substitutions within the Fc region, resulting in increased Fcγ receptor affinity), humanized, anti-CD19 monoclonal antibody. Developed by MorphoSys AG, under a license from Xencor, it received accelerated approval (in July 2020) for use in combination with lenalidomide as a treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT). It is the first therapy to be approved as a second-line treatment for this patient population in the USA. The recommended dose of tafasitamab is 12 mg per kg of bodyweight, administered via an intravenous infusion. A regulatory assessment for tafasitamab plus lenalidomide for the treatment of adults with relapsed or refractory DLBCL is currently underway in the EU. Tafasitamab is also being clinically investigated as a therapeutic option in various other B-cell malignancies, including follicular lymphoma and other indolent non-Hodgkin's lymphoma. This article summarizes the milestones in the development of tafasitamab leading to this first approval for its use in combination with lenalidomide in adults with relapsed or refractory DLBCL.

6. United States pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2021] Tafasitamab is a humanized monoclonal antibody that binds to the CD19 antigen, which is expressed in tumor cells from patients with diffuse large B-cell lymphoma (DLBCL). On June 24, 2021, a positive opinion for a conditional marketing authorization was issued by the European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP) for tafasitamab, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory DLBCL who are ineligible for autologous stem cell transplantation. Tafasitamab was evaluated in the phase 2 single-arm, multicenter, open-label L-MIND clinical trial. The primary endpoint of this trial was objective response rate (ORR). The best ORR, achieved at any time during the study, was 56.8% (95% confidence interval: 45.3%-67.8%), and the median duration of response was 34.6 months (95% confidence interval: 26.1-not reached). The most frequently reported adverse events by system organ class were infections and infestations (72.8%; grade ≥3: 29.6%), blood and lymphatic system disorders (65.4%; grade ≥3: 56.8%), gastrointestinal disorders (64.2%; grade ≥3: 2.5%), and general disorders and administration site conditions (58.0%; grade ≥3: 8.6%). The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the CHMP.

7. England pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. [2018] Lenalidomide (CC-5013; Revlimid) represents one compound in a category of new medications known as immunomodulatory drugs. These compounds are thalidomide derivatives. Through relatively minor structural modifications, the potency of the medication is improved compared with the parent compound, and the side-effect profile has changed considerably. The neurologic toxicity and pro-thrombotic effects of thalidomide are reduced in the structural analog, although concerns regarding pro-thrombotic effects are still present when lenalidomide is combined with dexamethasone. Data supporting lenalidomide's use in myelodysplastic syndrome and multiple myeloma has been published over the past several years and presented at the May 2005 meeting of the American Society of Clinical Oncology. Further trials are ongoing for many other malignancies. This report will review the preclinical and clinical results of the investigations with this exciting new therapeutic, its toxicities and future prospects.

8. Italy pubmed.ncbi.nlm.nih.gov

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. [2021] Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.