Rituximab + Tafasitamab + NK Cells for Non-Hodgkin's Lymphoma

Not yet recruiting at 1 trial location

Overseen By Paolo Caimi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Paolo Caimi, MD

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Active malignancy, Heart failure, HIV, Hepatitis, CNS pathology, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial targets individuals with B-cell non-Hodgkin's lymphoma (a type of blood cancer) that hasn't responded to at least two different treatments. The study aims to determine the optimal dose of a new therapy using NK cells (a type of immune cell that fights cancer), combined with the drugs Rituximab and Tafasitamab. Participants will also receive a drug called IL-2 to potentially enhance the treatment's effectiveness. It suits those with these specific types of lymphoma whose disease persists despite previous treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that less than 28 days must have passed since any prior treatment with investigational agents, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using Rituximab, Tafasitamab, and donor NK cells together is generally safe. NK cells, a type of immune cell, do not cause graft-versus-host disease, where donor cells attack the body, according to studies. This means they are usually well-tolerated. When combined with Rituximab and Tafasitamab, these treatments have been tested without major safety concerns.

Tafasitamab helps destroy cancer cells and has been studied in people with non-Hodgkin's lymphoma. These studies did not find any unexpected safety issues. Since Rituximab and Tafasitamab are already used to treat certain types of lymphoma, their safety is well-known.

Although NK cells are still being researched, the combination with Rituximab and Tafasitamab has shown promising safety results. Participants in trials have generally handled these treatments well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for Non-Hodgkin's Lymphoma because it harnesses the power of natural killer (NK) cells in a novel way. Unlike standard treatments that primarily use chemotherapy or monoclonal antibodies like Rituximab alone, this approach combines Rituximab and Tafasitamab with allogeneic NK cells. NK cells are a type of immune cell that can directly target and destroy cancer cells, potentially enhancing the efficacy of the treatment. This combination aims to offer a more robust attack on cancer by enlisting the body's immune system to fight alongside conventional therapies, offering hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for non-Hodgkin's lymphoma?

In this trial, participants will receive a combination of Rituximab, Tafasitamab, and donor NK cells to treat B-cell non-Hodgkin's lymphoma (NHL) that has returned or resisted other treatments. Research shows that combining Rituximab and Tafasitamab with donor NK cells may enhance treatment effectiveness. Studies have found that Tafasitamab can help the body's immune cells kill NHL cells, and when combined with donor NK cells, this treatment has destroyed more cancer cells. In some cases, Tafasitamab alone showed a 26% response rate in patients with certain types of NHL. These findings suggest that this combination therapy could be effective for those whose lymphoma hasn't responded to other treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

Paolo Caimi, MD

Principal Investigator

Case Comprehensive Cancer Center, Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for people with B-cell non-Hodgkin's lymphoma that hasn't improved after at least two treatments. Participants should be able to receive intensive chemotherapy and have no other treatment options available.

Inclusion Criteria

Participants must have measurable disease as defined by Lugano 2014 criteria for NHL or iwCLL 2018 criteria for CLL

My organs are functioning well.

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

I have HIV/AIDS.

Pregnant or breastfeeding women

Less than 28 days elapsed between prior treatment with investigational agent(s) and study enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to NK cell infusion

1 week

Treatment

Participants receive Allogeneic NK cells, Tafasitamab, and Interleukin-2 (IL-2) by intravenous infusion

28 days per cycle

Multiple visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic NK cells
• Rituximab
• Tafasitamab

Trial Overview The study tests a combination of allogeneic NK cells, IL-2, Tafasitamab, and Rituximab in patients with relapsed or refractory NHL. It aims to find the best dose of NK cells when used with these drugs over approximately one year.

How Is the Trial Designed?

Group I: Rtx + Tafasitamab in combination with allogeneic NK Cells Experimental Treatment 5 Interventions

This arm includes dose escalation for allogeneic NK cells. All other therapies are given according to standard of care. The length of the treatment period is 28 days per cycle. Participants will be expected to complete one cycle and may have the option to complete a second cycle unless there is evidence of disease progression at the end of the first cycle.

Who Is Running the Clinical Trial?

Paolo Caimi, MD

Lead Sponsor

Trials

5

Recruited

170+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07225439

Rituximab (Rtx) + Tafasitamab in Combination With ... The purpose of this study is to identify the recommended dose of allogeneic NK cells in combination with IL-2, Tafasitamab and Rituximab for the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9519642/

Tafasitamab mediates killing of B-cell non-Hodgkin's ... Tafasitamab induced killing of NHL cell lines and primary CLL and MCL cells by γδ T cells · Combination of tafasitamab and allogeneic NK cells led to increased ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT07225439

Rituximab (Rtx) + Tafasitamab in Combination With ... Rituximab (Rtx) + Tafasitamab in Combination With Allogeneic NK Cells for Treatment of Relapsed/Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL) ... Data.

4. tandfonline.com tandfonline.com/doi/full/10.1080/21645515.2024.2309701

Tafasitamab for the treatment of patients with diffuse large ... In the DLBCL cohort, the response rate was 26% and median DoR was 20.1 months; median PFS was 2.7 months (95% confidence interval [CI] 2.1–13.2 months). Similar ...

5. ashpublications.org ashpublications.org/blood/article/146/15/1782/546730/Treatment-of-relapsed-and-refractory-follicular

Treatment of relapsed and refractory follicular lymphoma There was a 79% reduction in the risk of death or disease progression compared with those treated with only rituximab and lenalidomide. However, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/761163Orig1s000MultidisciplineR.pdf

761163Orig1s000 - accessdata.fda.gov arm trial evaluating single-agent tafasitamab in patients with relapsed or refractory non-Hodgkin's Lymphoma. The ORR in the 35 patients ...