FT522 + Rituximab for B-Cell Lymphoma

No longer recruiting at 6 trial locations

Overseen By Fate Trial Disclosure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fate Therapeutics

Must be taking: Rituximab

Must not be taking: Immunosuppressants, CNS medications

Disqualifiers: Pregnancy, Organ transplant, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with B-cell lymphoma, a type of blood cancer that has returned or not responded to previous treatments. The study examines the safety and tolerability of FT522, an iPSC-derived CAR NK cell product candidate, when combined with rituximab, a drug already used for this condition. Participants will be divided into two groups: one receiving additional chemotherapy and the other not. This trial may suit those who have tried other anti-CD20 treatments without success and have a type of B-cell lymphoma measurable on scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any biological therapy, chemotherapy (except for rituximab), or investigational therapy within 2 weeks before starting the study. You also cannot be on systemic immunosuppressive therapy from 5 days before to 29 days after starting the study, except for certain corticosteroids.

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

Research has shown that FT522, when used with rituximab, is still under careful study for safety. FT522 is a type of cell therapy that uses special cells to target and fight cancer. In earlier studies, some patients tolerated it well. However, as this is a phase 1 study, the primary goal is to assess its safety.

Rituximab is an established treatment already approved for certain types of cancer, so its safety is well-known. However, researchers are still learning about possible side effects or risks associated with FT522.

Phase 1 trials mark the beginning of research. They help determine if a treatment is safe and how it might work in people. While early results can be promising, unknowns may still exist. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about FT522 for B-cell lymphoma because it offers a novel approach by using engineered natural killer (NK) cells to target cancer. Unlike traditional treatments like chemotherapy and monoclonal antibodies alone, FT522 is designed to enhance the body's immune response specifically against cancer cells. Furthermore, when combined with rituximab, this treatment aims to improve efficacy by leveraging the unique properties of NK cells to potentially boost anti-cancer activity. This dual approach could lead to better outcomes for patients with fewer side effects compared to conventional therapies.

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

Research has shown that FT522 is a promising new treatment for relapsed/refractory B-cell lymphoma. FT522 is a form of immunotherapy, which helps the immune system fight cancer. It uses natural killer cells, a part of the immune system, to target and attack cancer cells. Early studies suggest FT522 is effective due to a special feature that enhances its function. In this trial, participants will receive FT522 combined with rituximab, a well-known cancer treatment. Some participants will receive this combination with chemotherapy, while others will receive it without chemotherapy. Previous results indicate that this combination could help control the disease and shrink tumors. While more research is needed, these early findings offer hope for those considering participation in clinical trials. ^{1 2 3 4 5}

Who Is on the Research Team?

Study Director

Principal Investigator

Fate Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with B-cell lymphoma who've tried at least one treatment including an anti-CD20 antibody, but still need therapy. They must have a type of tumor that shows up on certain scans and can't be pregnant or breastfeeding. Participants should be relatively healthy, not too underweight, and able to use birth control if necessary.

Inclusion Criteria

I agree to use birth control as required by the study.

I have a type of B-cell lymphoma and my cancer has come back or didn't respond to treatment.

Exclusion Criteria

I have received an organ transplant from another person.

I haven't had certain cancer treatments or experimental drugs in the last 2 weeks.

Any medical condition or clinical laboratory abnormality that per investigator or medical monitor judgement, precludes safe participation in and completion of the study, or that could affect compliance with protocol conduct or interpretation of results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FT522 in combination with rituximab, with or without chemotherapy, to evaluate safety and determine the recommended phase 2 dose

4 weeks

Multiple visits during Cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Cyclophosphamide
• Fludarabine
• FT522
• Rituximab

Trial Overview The study tests FT522 cells combined with the drug rituximab in people whose B-cell lymphoma has come back or didn't respond to treatment. It's looking for the safest dose that works best (RP2D). Some may get extra chemo drugs like fludarabine or bendamustine before this combo.

How Is the Trial Designed?

Group I: Regimen B Experimental Treatment 2 Interventions

Participants receive FT522 in combination with rituximab (or a rituximab biosimilar approved by a local health authority) without chemotherapy.

Group II: Regimen A Experimental Treatment 5 Interventions

Participants receive FT522 in combination with rituximab (or a rituximab biosimilar approved by a local health authority) with chemotherapy.

Who Is Running the Clinical Trial?

Fate Therapeutics

Lead Sponsor

Trials

22

Recruited

1,200+

Published Research Related to This Trial

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

Rituximab has shown a response rate of approximately 70% as a first-line treatment for indolent lymphoma, with low toxicity and the ability to retreat patients successfully, leading to longer remission durations.

Combination therapies using rituximab with chemotherapy have resulted in high complete response rates and a greater likelihood of molecular complete remission compared to chemotherapy alone, indicating its potential to enhance treatment outcomes in lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy in lymphoid malignancies. Hainsworth, JD.[2019]

Rituximab monotherapy can induce complete responses in patients with follicular lymphoma, and it significantly affects the dynamics of natural killer (NK) cells, leading to a rapid decrease in their numbers but an increase in their activation markers.

The effectiveness of rituximab on NK cells varies based on the pre-existing diversity of the NK cell repertoire, with patients having adaptive NKG2C+ NK cells showing less functional loss during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic and Intra-Nodal Activation of NK Cells After Rituximab Monotherapy for Follicular Lymphoma. Enqvist, M., Jacobs, B., Junlén, HR., et al.[2020]

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]

Obinutuzumab treatment in patients with chronic lymphocytic leukemia and follicular lymphoma led to a significant decrease in natural killer (NK) cell levels in peripheral blood, dropping below the normal range.

Subcutaneous rituximab resulted in a less pronounced reduction of NK cells compared to intravenous rituximab, suggesting that the method of administration may influence NK cell levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army. García-Muñoz, R., Nájera, MJ., Feliu, J., et al.[2022]

Rituximab can activate unlicensed NK cells, which are usually less responsive, enhancing their role in fighting tumors, particularly in patients with follicular lymphoma.

A specific 'missing ligand' genotype associated with unlicensed NK cells was linked to improved progression-free survival in 101 patients, suggesting it could be a useful biomarker for personalizing treatment with rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CALGB 150905 (Alliance): rituximab broadens the antilymphoma response by activating unlicensed NK cells. Du, J., Lopez-Verges, S., Pitcher, BN., et al.[2021]

Combining cytokine-induced killer (CIK) cells with anti-CD20 monoclonal antibodies, specifically GA101 and rituximab, significantly enhances the cytotoxic activity against B-cell non-Hodgkin lymphoma (B-NHL), with GA101 showing a 35% increase in effectiveness compared to a 15% increase with rituximab.

The enhanced cytotoxicity is primarily due to antibody-dependent cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC), suggesting that using GA101 in combination with CIK cells could be a promising strategy for improving treatment outcomes in B-NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced killing of human B-cell lymphoma targets by combined use of cytokine-induced killer cell (CIK) cultures and anti-CD20 antibodies. Pievani, A., Belussi, C., Klein, C., et al.[2022]

In a study of 7 patients with primary cutaneous B-cell lymphoma who had relapsed after chemotherapy, the combination of intravenous rituximab and single-dose cyclophosphamide resulted in an impressive overall response rate of 85.7%, with 5 patients achieving complete remission.

The treatment was well tolerated, and after a median follow-up of 13 months, most patients remained disease-free for significant durations, indicating promising efficacy and safety for this approach in managing relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. Fierro, MT., Savoia, P., Quaglino, P., et al.[2019]

Blocking inhibitory KIRs on NK cells with anti-KIR antibodies enhances their ability to kill lymphoma cells, increasing spontaneous cytotoxicity.

Combining anti-KIR treatment with rituximab significantly boosts NK-cell-mediated destruction of lymphoma in both laboratory and animal models, suggesting a promising new strategy for lymphoma therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Kohrt, HE., Thielens, A., Marabelle, A., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6543/528232/Safety-and-Efficacy-of-FT522-a-First-in-Class

Safety and Efficacy of FT522, a First-in-Class, Multi-Antigen ... FT522 is an iPSC-derived, off -the-shelf, natural killer (iNK) cell therapy that expresses a novel alloimmune defense receptor (ADR), which is ...

2. ir.fatetherapeutics.com ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-ft522-shelf-adr-armed-car-nk-cell

Fate Therapeutics Highlights FT522 Off-the-shelf, ADR-armed ... FT522 is the Company's off-the-shelf, CD19-targeted chimeric antigen receptor (CAR) natural killer (NK) cell product candidate that incorporates multiple novel ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124093698

Safety and Efficacy of FT522, a First-in-Class, Multi-Antigen ... FT522 is an iPSC-derived, off-the-shelf, natural killer (iNK) cell therapy that expresses a novel alloimmune defense receptor (ADR).

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.70094_467

467 | SAFETY AND EFFICACY OF FT522, AN OFF‐THE‐ ... Introduction: FT522 is an iPSC-derived, off -the-shelf, natural killer (iNK) cell therapy that expresses a novel alloimmune defense receptor ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05950334

FT522 With Rituximab in Relapsed/Refractory B-Cell ... ... FT522 iPSC-derived CAR NK Cell Program Data...In a preclinical in vivo biodistribution study, FT522 showed dose-dependent trafficking, infiltration, and ...