CAR T-Cell Therapy for Non-Hodgkin's Lymphoma

Overseen By FHCC Immunotherapy Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Fred Hutchinson Cancer Research Center

Must be taking: BTK inhibitors, BCL-2 inhibitors

Must not be taking: Anti-CD19, Anti-CD20

Disqualifiers: Autoimmune disease, HIV, Cardiovascular, CNS pathology, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and assess the safety of a treatment using modified T-cells for individuals with certain types of non-Hodgkin's lymphoma, a cancer affecting the lymphatic system. It targets patients whose cancer has returned or did not respond to previous treatments. Participants with B-cell non-Hodgkin lymphoma that has either recurred or resisted prior treatments might be suitable candidates, particularly if they have experienced this after earlier therapies. The treatment involves autologous T cells engineered to express a CD20-specific chimeric antigen receptor, known as CAR T-cell therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not be on corticosteroid therapy at a dose of 15 mg or more per day of prednisone or the equivalent, and certain investigational agents and treatments must be stopped before enrollment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that a new treatment using CD20-specific CAR T cells is being tested for safety in patients with relapsed or refractory B cell non-Hodgkin lymphoma. In earlier studies, some patients experienced side effects such as fever, low blood cell counts, and infections. However, most tolerated the treatment well.

As this study is in its early stages, the main goal is to determine the best dose and monitor side effects. Safety information is still being gathered and reviewed. Prospective participants should understand that while there are possible risks, researchers are carefully studying these to ensure the best results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-Hodgkin's lymphoma?

CAR T-cell therapy is unique because it uses the patient's own T cells, which are re-engineered to specifically target and destroy cancer cells expressing the CD20 antigen. Unlike traditional treatments for Non-Hodgkin's Lymphoma, like chemotherapy and monoclonal antibodies, this therapy directly modifies the immune system to recognize and attack cancer cells. Researchers are excited about this treatment because it represents a personalized approach, potentially leading to more effective and long-lasting cancer control with fewer side effects associated with conventional therapies.

What evidence suggests that this treatment might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that CD20-specific CAR T-cell therapy, which participants in this trial will receive, holds promise for treating certain types of lymphoma. In one study, all patients with relapsed or hard-to-treat B-cell non-Hodgkin lymphoma experienced some improvement, with 80% showing no signs of cancer afterward. Another study found positive results in patients who did not respond to other treatments, highlighting the potential of CD20-targeted therapy. These findings suggest this treatment could be very effective for people whose lymphoma hasn't improved with previous treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Mazyar Shadman

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with certain types of B cell non-Hodgkin lymphoma or chronic lymphocytic leukemia that have relapsed or are refractory. They must understand the study, be willing to use contraception, and meet health criteria including organ function and performance status. Excluded are those with recent significant heart disease, active autoimmune diseases needing steroids, HIV positive individuals, pregnant or breastfeeding women, and those with other progressing cancers.

Inclusion Criteria

I meet the requirements for a specific type of chemotherapy to reduce my white blood cells.

I can understand and sign the consent form.

My diagnosis was confirmed by a pathology review at a specified center.

Exclusion Criteria

I have another cancer that is getting worse or needs treatment.

I am on medication to suppress my immune system due to an autoimmune disease.

You have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Pre-treatment

Patients undergo leukapheresis and may receive treatment for disease control, followed by cyclophosphamide and possibly fludarabine IV

1-2 weeks

CAR T Cell Infusion

Patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes

1 day

Active Monitoring

Participants are monitored for dose-limiting toxicities and other adverse events

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term Follow-up

Participants are followed up for a minimum of 15 years to assess long-term outcomes

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor

Trial Overview

The trial is testing genetically modified T-cells targeting CD20 in patients with specific B cell malignancies. It aims to determine the optimal dose for safety and effectiveness. The process includes leukapheresis (to collect white blood cells), followed by laboratory biomarker analysis, chemotherapy conditioning (with Cyclophosphamide and Fludarabine Phosphate), then infusion of engineered T-cells.

How Is the Trial Designed?

Group I: Treatment (CD20-specific CAR T cell, chemotherapy) Experimental Treatment 5 Interventions

Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Mustang Bio

Industry Sponsor

Trials

4

Recruited

80+

Published Research Related to This Trial

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

CAR T cell therapy has shown remarkable success in treating B-cell malignancies, but it faces significant challenges when targeting solid tumors due to the unique characteristics of their microenvironments.

Recent advancements in CAR T cell engineering aim to overcome these challenges by developing smarter CAR T cells that enhance efficacy and reduce adverse effects, paving the way for improved cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells. Elahi, R., Khosh, E., Tahmasebi, S., et al.[2019]

CAR T-cell therapy, particularly targeting CD19, has shown promising results in treating B-cell malignancies like B-ALL, with high rates of remission reported in clinical trials.

Despite its effectiveness, CAR T-cell therapy carries risks of significant neurotoxicity and cytokine release syndrome, necessitating careful management and further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular Immunotherapy in B-Cell Malignancy. Schwarzbich, MA., Witzens-Harig, M.[2018]

Approximately 20% of lymphoma patients develop resistance to conventional therapies, leading to a poor prognosis with a median survival of only 6.3 months, highlighting the need for effective new treatments.

T-cell immunotherapy, particularly CAR T-cell therapy targeting the CD19 antigen, has shown remarkable efficacy in inducing complete and durable responses in patients with chemotherapy-refractory B-cell non-Hodgkin lymphoma, and has been approved by the FDA for this use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of chimeric antigen receptor T cells in patients with non-Hodgkin lymphoma. Lulla, PD., Hill, LC., Ramos, CA., et al.[2021]

CAR-T cell therapy demonstrated a high overall response rate of 85.2% in 27 patients with relapsed/refractory B cell non-Hodgkin lymphoma, with a complete response rate of 63.0% after a median follow-up of 32 months.

While adverse reactions like cytokine release syndrome and myelosuppression were common, they were manageable, and patients achieving a complete response had significantly better long-term survival rates compared to those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy of CAR-T cell therapy for patients with relapsed/refractory B cell non-Hodgkin lymphoma. Fu, S., Hu, Y., Huang, H.[2022]

CAR T cells have shown significant clinical effectiveness in treating blood cancers, but their success in solid tumors has been less impressive, highlighting the need for further research in this area.

While CAR T cell therapy can lead to serious side effects like cytokine release syndrome and neurological toxicity, some theoretical risks have not yet been observed in clinical settings, emphasizing the importance of managing known toxicities for safe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. Bonifant, CL., Jackson, HJ., Brentjens, RJ., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

CAR T cell therapy targeting CD19 has shown remarkable efficacy in treating relapsed and refractory B-cell acute lymphoblastic leukemia, with most patients achieving complete remissions.

Despite its effectiveness, CAR T cell therapy is associated with significant risks of toxicity, including cytokine-release syndrome and neurotoxicity, which can be managed with treatments like tocilizumab and corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted T Cells for Hematologic Malignancies: Clinical Experience to Date. Davila, ML., Sauter, C., Brentjens, R.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9646688/

Pre-clinical efficacy of CD20-targeted chimeric antigen ...

For instance, liso-cel achieved the best overall response rate of 80% and the best complete response rate of 59% [12]. Although CD19-targeting ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35691818/

CD20-specific chimeric antigen receptor-expressing T cells ...

This prospective study aimed to assess the effectiveness and toxicity of CD20 CAR T cells in R/R B-NHL patients previously treated with rituximab.

3.

frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1567149/full

Case Report: Bispecific CD20/CD30-targeted chimeric ...

We report that a patient with bulky transformed follicular lymphoma was successfully treated with CD20/CD30-directed CAR-T cells.

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1465324922006405

CD20-specific chimeric antigen receptor-expressing T cells ...

An overall response rate of 100% was shown in enrolled patients, with 12 (80%) achieving complete remission and three (20%) achieving partial remission for the ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.2508

Safety and efficacy of a novel anti-CD20 chimeric antigen ...

C-CAR066 has shown a favorable safety profile and promising efficacy in patients with r/r B-NHL following failure of CD19 CAR-T therapy.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03277729

NCT03277729 | A Phase I/II Study to Evaluate the Safety of ...

The purpose of this research is to find the best dose of genetically modified T-cells, to study the safety of this treatment, and to see how well it works ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3350361/

CD20-specific adoptive immunotherapy for lymphoma ...

Recent clinical trial data demonstrate that modification of T cells with chimeric antigen receptors (CARs) is a promising strategy. T cells containing CARs with ...

8.

nature.com

nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ...

Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

9.

clin.larvol.com

clin.larvol.com/trial-detail/NCT03277729

Fred Hutchinson Cancer Center

A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor ...