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

53 Participants Needed

Trial Summary

What is the purpose of this trial?

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 in treating patients with B cell non-Hodgkin lymphoma that has come back (relapsed) or did not respond to previous treatment (refractory).

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.

What data supports the effectiveness of this treatment for non-Hodgkin's lymphoma?

Research shows that CAR T-cell therapy, which involves modifying a patient's own T cells to target cancer cells, has been effective in treating B-cell non-Hodgkin lymphoma, especially in patients who did not respond to other treatments. Studies have demonstrated that this approach can lead to complete and lasting responses in some patients. ^{1 2 3 4 5}

Is CAR T-Cell Therapy safe for humans?

CAR T-Cell Therapy has shown safety in clinical trials, but it can cause side effects like cytokine release syndrome (a severe immune reaction) and neurological issues. These side effects are manageable with proper medical care. ^{2 6 7 8 9}

How is CAR T-Cell Therapy for Non-Hodgkin's Lymphoma different from other treatments?

CAR T-Cell Therapy is unique because it uses a patient's own T cells, which are modified to specifically target and kill cancer cells by recognizing a protein called CD20 on their surface. This approach is different from traditional chemotherapy as it is a form of immunotherapy that harnesses the body's immune system to fight cancer, offering hope for patients who do not respond to conventional treatments. ^{1 2 4 5 10}

Research Team

Mazyar Shadman

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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.

I am taking 15 mg or more of prednisone daily.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Long-term efficacy of CAR-T cell therapy for patients with relapsed/refractory B cell non-Hodgkin lymphoma. [2022]

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

CARs and cancers: questions and answers. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Programming CAR-T cells to kill cancer. [2019]

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

The use of chimeric antigen receptor T cells in patients with non-Hodgkin lymphoma. [2021]

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

Recent advances in engineered T cell therapies targeting B cell malignancies. [2018]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

CD19-Targeted T Cells for Hematologic Malignancies: Clinical Experience to Date. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cellular Immunotherapy in B-Cell Malignancy. [2018]

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

Toxicity and management in CAR T-cell therapy. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells. [2019]