Tafasitamab + Rituximab for Lymphoma

Recruiting at 2 trial locations

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Timothy Voorhees

Disqualifiers: Uncontrolled infection, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well tafasitamab and rituximab work for front-line treatment of patients with post-transplant lymphoproliferative disorder. Post-transplant lymphoproliferative disorder (PTLD) is the name for types of lymphoma that sometimes develop in people who have had a transplant. It can affect people who are taking medicines to suppress their immune system. Tafasitamab injection is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving the combination of tafasitamab and rituximab may work better in treating patients with post-transplant lymphoproliferative disorder.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it allows certain treatments like palliative radiation, steroids, antiviral therapy, and reduced immunosuppression. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Tafasitamab and Rituximab for treating lymphoma?

Rituximab, a key component of the treatment, has shown significant benefits in treating non-Hodgkin's lymphoma, improving survival rates when combined with chemotherapy. It is effective as a single agent and in combination with other therapies, suggesting potential effectiveness when combined with Tafasitamab. ^{1 2 3 4 5}

What is known about the safety of Tafasitamab + Rituximab for Lymphoma?

Rituximab is generally well tolerated, but some patients may experience infusion reactions like chills and fever, and rare serious side effects like heart issues. It may also increase the risk of infections, including hepatitis B reactivation, so screening and preventive measures are important. The safety profile of rituximab biosimilars is comparable to the original, with similar rates of adverse events. ^{6 7 8 9 10}

What makes the drug Tafasitamab + Rituximab unique for treating lymphoma?

The combination of Tafasitamab and Rituximab is unique because it pairs two monoclonal antibodies that target B-cells, potentially enhancing the immune system's ability to fight lymphoma. This combination may offer a novel approach compared to using Rituximab alone, which has been effective but typically used with chemotherapy or other agents. ^{1 11 12 13 14}

Research Team

Timothy J. Voorhees, MD, MSCR

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

Adults who've had an organ transplant and developed a type of lymphoma called post-transplant lymphoproliferative disorder (PTLD) are eligible. They should have measurable disease, acceptable organ function tests, no prior PTLD therapy except for certain treatments like antivirals or steroids, and not be pregnant or breastfeeding. People with HIV can join if it's under control.

Inclusion Criteria

You have given written agreement to partake in the study, and have authorized access of your healthcare information under HIPAA regulations.

My kidney function, measured by creatinine clearance, is adequate.

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

Exclusion Criteria

I have had progressive multifocal leukoencephalopathy in the past.

I have active hepatitis B but am on entecavir or have an undetectable viral load.

You have a medical condition or laboratory results that make it unsafe for you to participate in this study or could make it difficult to understand the study results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafasitamab and rituximab intravenously or subcutaneously for 4 cycles of weekly treatments

4 weeks

4 visits (in-person)

Consolidation

Participants who achieve CR or PR may receive additional tafasitamab and rituximab every 3 weeks for 4 cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Rituximab
• Tafasitamab

Trial Overview The trial is testing the effectiveness of two monoclonal antibodies, tafasitamab and rituximab, in treating PTLD. These drugs help the immune system target and kill cancer cells. Participants will receive injections of these medications to see if they work better together as a first-line treatment.

Participant Groups

Group I: Treatment (tafasitamab, rituximab) Experimental Treatment 6 Interventions

Patients receive tafasitamab IV and rituximab IV or SC on study. Patients who have CR or PR after 4 cycles may receive additional tafasitamab and rituximab on study. Patients also undergo PET or CT, biopsy, and collection of blood samples throughout the trial.

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

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

Timothy Voorhees

Lead Sponsor

Trials

3

Recruited

70+

Findings from Research

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Rituximab has been shown to significantly improve progression-free and overall survival in patients with non-Hodgkin's lymphoma, based on a systematic review of 23 randomized controlled trials.

The treatment is particularly effective when added to chemotherapy for aggressive B-cell lymphomas and for both initial and subsequent treatments of indolent B-cell lymphomas, as well as for maintenance therapy in responding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in lymphoma: a systematic review and consensus practice guideline from Cancer Care Ontario. Cheung, MC., Haynes, AE., Meyer, RM., et al.[2018]

The addition of rituximab, a monoclonal antibody, to conventional chemotherapy (R-CHOP regimen) significantly enhances treatment outcomes for patients with diffuse large B-cell lymphoma (DLBCL), improving response rates, progression-free survival (PFS), and overall survival (OS).

Rituximab also boosts response rates and PFS in mantle cell lymphoma (MCL) and improves outcomes in follicular lymphoma (FL), highlighting its critical role in enhancing the efficacy of chemotherapy across various types of non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma. Kahl, B.[2021]

Rituximab, an anti-CD20 monoclonal antibody, shows high efficacy in treating low-grade lymphoma, with response rates of 50-60% in relapsed cases and 60-75% as a first-line treatment, and even higher rates (85-95%) when combined with chemotherapy.

The mechanism of action for rituximab includes complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and its dosing may be optimized by monitoring serum levels to account for individual patient variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of low-grade B-cell lymphoma with the monoclonal antibody rituximab. Dillman, RO.[2019]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

Rituximab, a monoclonal antibody used for treating certain cancers and autoimmune diseases, is generally well tolerated but can cause serious side effects, including rare but life-threatening cardiovascular events like myocardial infarction.

A case study of a 58-year-old man revealed that he experienced a ST-elevation myocardial infarction during rituximab treatment, highlighting the need for careful screening for ischemic heart disease in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. Sharif, K., Watad, A., Bragazzi, NL., et al.[2022]

Rituximab, a chimeric anti-CD20 monoclonal antibody, is a standard treatment for non-Hodgkin's lymphoma (NHL) and has been used in over 300,000 patients worldwide, demonstrating its widespread acceptance and efficacy.

The combination of rituximab with standard CHOP chemotherapy is approved for treating diffuse large B-cell lymphoma, and while it is generally well tolerated, common side effects include infusion-related reactions like chills and fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. Boye, J., Elter, T., Engert, A.[2020]

Rituximab is an effective anti-CD20 monoclonal antibody that has demonstrated single-agent activity in treating B-cell non-Hodgkin's lymphoma, with a long serum half-life and low immunogenicity, making it a promising therapy.

While initial infusions can cause mild infusion symptoms and temporary B-cell depletion, these effects are generally manageable and not linked to immunodeficiency, supporting its use alongside or after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and phase I and II trials of rituximab. Maloney, DG.[2015]

Rituximab has been shown to be very safe over more than 10 years of use, but it can significantly increase the risk of infections, especially in patients with low-grade lymphoma or severe immunodeficiency, such as those with HIV or on immunosuppressive therapies.

The most critical infection associated with rituximab is hepatitis B reactivation, which can lead to severe liver failure; therefore, screening for hepatitis B and considering preemptive antiviral treatment is essential for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-associated infections. Gea-Banacloche, JC.[2020]

Rituximab, a chimeric monoclonal anti-CD20 antibody, shows enhanced effectiveness when combined with interferon alpha, leading to higher complete response rates and longer response durations in treatment.

While other immunomodulatory agents like interleukin-2 and Epratuzumab show potential for synergy with Rituximab, further randomized trials are needed to confirm their efficacy compared to Rituximab alone, particularly in indolent lymphomas where chemotherapy might be unnecessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of anti-CD20 monoclonal antibody in association with immunomodulatory agents]. Bosly, A.[2017]

Rituximab is an effective treatment for relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma, showing an overall response rate of 48% in a multicenter trial with 166 patients.

The treatment is well tolerated, primarily causing mild adverse events, and has a median time to progression of 13.2 months for responders, making it a feasible outpatient therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Grillo-López, AJ., White, CA., Varns, C., et al.[2020]

In a study of 18 elderly patients with non-Hodgkin's lymphoma, the combination of rituximab and CHOP showed a high response rate of 91%, indicating its potential effectiveness as a treatment option.

While the overall survival and disease-free survival rates were slightly better in the rituximab plus CHOP group (91%) compared to CHOP alone (83% overall survival), the differences were not statistically significant, suggesting that further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck. Manolopoulos, L., Gomatos, IP., Leandros, E., et al.[2015]

A 56-year-old man developed dilated cardiomyopathy after receiving rituximab and bendamustine for chronic lymphocytic leukemia, highlighting a potential serious cardiovascular side effect of rituximab.

Despite the adverse reaction, the patient fully recovered after treatment with medications for cardiomyopathy and supportive care, emphasizing the importance of monitoring for such effects in patients undergoing rituximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversible Cardiomyopathy after Rituximab Treatment in a Chronic Lymphocytic Leukemia Patient. Girkar, N., Zaki, S., Pawar, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Rituximab in lymphoma: a systematic review and consensus practice guideline from Cancer Care Ontario. [2018]

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

Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma. [2021]

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

Treatment of low-grade B-cell lymphoma with the monoclonal antibody rituximab. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. [2019]

6. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

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

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. [2022]

8. England pubmed.ncbi.nlm.nih.gov

An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. [2020]

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

Preclinical and phase I and II trials of rituximab. [2015]

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

Rituximab-associated infections. [2020]

11. France pubmed.ncbi.nlm.nih.gov

[Role of anti-CD20 monoclonal antibody in association with immunomodulatory agents]. [2017]

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

Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. [2020]

13. Greece pubmed.ncbi.nlm.nih.gov

Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck. [2015]

14. England pubmed.ncbi.nlm.nih.gov

Reversible Cardiomyopathy after Rituximab Treatment in a Chronic Lymphocytic Leukemia Patient. [2022]