CAR-T Therapy for B-Cell Lymphoma

Overseen By Marcus Butler, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune, Immunodeficiency, Transplant, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

19 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called TBI-2001, a type of CAR-T therapy, for people with certain types of B-cell lymphoma that haven't responded to other treatments. It examines whether TBI-2001 is safe and effective when administered after chemotherapy. The trial seeks participants who have tried at least two other treatments for their B-cell lymphoma and have been informed that their disease is hard to cure.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol suggests that you may need to stop certain medications before apheresis and lymphodepleting chemotherapy, following specific guidelines. However, if you are on targeted or biological therapies that don't affect the collection of lymphocytes, you might not need a washout period, but this requires approval from the Sponsor.

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

Research has shown that CD19 CAR T-cell therapies, such as TBI-2001, have been tested for safety in treating B-cell lymphoma that has returned or is unresponsive to other treatments. Some studies suggest these therapies can be effective, but reports indicate potential side effects. Common side effects include fever and low blood pressure.

This trial is a Phase 1 study, focusing primarily on safety. In Phase 1 trials, researchers assess how well participants tolerate the treatment and identify any side effects. Although early studies provide some safety information, further research is necessary to fully confirm safety in larger groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell lymphoma, which often include chemotherapy and monoclonal antibodies, TBI-2001 is unique because it uses CAR-T cell therapy. This approach involves engineering a patient's own T-cells to specifically target and destroy cancerous B-cells. Researchers are excited about TBI-2001 because it offers a personalized attack on cancer cells with the potential for greater precision and effectiveness. Additionally, the intravenous delivery of these modified cells after chemotherapy conditioning could lead to more durable remissions compared to traditional treatments.

What evidence suggests that TBI-2001 might be an effective treatment for B-cell lymphoma?

Research has shown that CAR-T cell therapy, such as TBI-2001, holds promise for treating B-cell lymphoma. This trial will administer TBI-2001, which uses specially modified immune cells, called CAR-T cells, to target and destroy cancer cells with the CD19 marker. Studies on similar therapies have shown positive results, with patients experiencing a significant decrease in cancer size and even complete remission. While data on TBI-2001 is still being gathered, it is based on successful methods used in other treatments targeting CD19. Early signs suggest that TBI-2001 could be effective for patients whose B-cell lymphoma has returned or not responded to other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Marcus Butler

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with CD19+ B-cell Lymphoma, CLL, or SLL who've had at least two prior treatments. They should be in good health with a life expectancy of more than 4 months and have not received cancer treatment within the last two weeks. Pregnant women, those with certain medical conditions or history of organ transplant requiring immunosuppression are excluded.

Inclusion Criteria

I have B cell cancer and have had at least 2 treatments before.

Phase Ib cohort will enroll CLL/SLL patients only

Life expectancy greater than 4 months

Exclusion Criteria

Pregnant or lactating women

Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation

I haven't had any cancer except skin cancer in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive conditioning chemotherapy with cyclophosphamide and fludarabine

1-2 weeks

Treatment

Participants receive TBI-2001 CAR-T cells intravenously following dose-escalation cohorts

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Long-term follow-up is conducted for 5 years following the infusion of TBI-2001

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• TBI-2001

Trial Overview The study tests TBI-2001 (a CAR-T therapy targeting CD19) along with Cyclophosphamide and Fludarabine in patients whose disease returned after treatment or didn't respond to previous therapies. It's an early-phase trial to check safety and effectiveness, gradually increasing doses to find the right amount.

How Is the Trial Designed?

Group I: Experimental: Dose Level 1 to 3 Experimental Treatment 3 Interventions

0.3 to 3 x 10\^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Takara Bio Inc.

Industry Sponsor

Trials

14

Recruited

270+

Published Research Related to This Trial

A 63-year-old patient with refractory EBV-positive diffuse large B-cell lymphoma developed interstitial pneumonitis 16 weeks after receiving CD19 CAR-T cell therapy, highlighting a rare but serious complication of this treatment.

The patient successfully recovered from the pneumonitis with intravenous immunoglobulin, emphasizing the need for careful monitoring and appropriate management of potential immunotherapy-related side effects in CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR-T Cell Therapy Induced Immunotherapy Associated Interstitial Pneumonitis: A Case Report. Sun, Z., Xie, C., Liu, H., et al.[2022]

The treatment of a patient with advanced follicular lymphoma using genetically modified T cells expressing a CAR targeting CD19 resulted in a dramatic regression of the lymphoma and a selective elimination of B-cell precursors from the bone marrow.

This approach led to the absence of blood B cells for at least 39 weeks post-infusion, indicating a successful and prolonged antigen-specific eradication of B-lineage cells, which was not solely due to the prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Kochenderfer, JN., Wilson, WH., Janik, JE., et al.[2023]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

In a study of 45 patients with active CNS lymphoma receiving CAR T-cell therapy, 68.9% showed a CNS response, with 40% achieving a complete response lasting an average of 11.4 months, indicating the therapy's efficacy in this challenging population.

While CAR T-cell therapy demonstrated a favorable safety profile, mild to severe neurotoxicity (ICANS) occurred in 42.2% and 15.6% of transfusions, respectively, with higher risks associated with secondary CNS lymphoma and certain pre-treatment factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells. Karschnia, P., Arrillaga-Romany, IC., Eichler, A., et al.[2023]

In a phase I study involving 10 patients with refractory diffuse large B-cell lymphoma (DLBCL), the anti-CD19 CAR T cell therapy (C-CAR011) demonstrated a 50% overall response rate at 12 weeks, indicating promising efficacy for this treatment.

The therapy showed a favorable safety profile, with 90% of patients experiencing cytokine release syndrome but no severe (grade ⩾ 3) cases or neurotoxicity, suggesting it is a safe option for patients with heavily treated DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. Fan, L., Wang, L., Cao, L., et al.[2022]

A new Phase I clinical trial at MD Anderson Cancer Center is investigating the safety and feasibility of using autologous T cells modified to express a CD19-specific chimeric antigen receptor (CAR) in patients with high-risk B-lymphoid malignancies undergoing hematopoietic stem-cell transplantation (HSCT).

This approach combines cell and gene therapies, utilizing a nonviral gene transfer method to create tumor-specific T cells, which may enhance treatment efficacy while minimizing the toxicities associated with traditional chemotherapy and radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. Kebriaei, P., Huls, H., Jena, B., et al.[2021]

A 61-year-old male patient with intravascular large B-cell lymphoma and CNS involvement achieved complete remission after receiving CAR T-cell therapy following a conditioning regimen and autologous stem cell transplantation.

The treatment was associated with only mild side effects, specifically grade 1 cytokine release syndrome, and no serious adverse events like neurotoxicity or pseudoprogression, suggesting that CAR T-cell therapy can be safely administered to patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. Yagi, Y., Kanemasa, Y., Ohigashi, A., et al.[2022]

In a study of 19 patients with relapsing B-cell lymphoma who received anti-CD19 CAR T-cell therapy, no new neurologic deficits or changes in brain MRI were observed two years post-treatment, indicating long-term neurologic safety.

Cognitive performance remained stable over the two years, even in patients who experienced acute neurotoxicity, and there was a significant reduction in anxiety scores, suggesting overall improvement in mental health after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. Ursu, R., Maillet, D., Belin, C., et al.[2023]

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.

Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-directed CAR T-cell therapy in B-cell NHL. Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]

In a study of 11,098 adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), 2.7% experienced severe neurologic adverse events (AEs) within 30 days of treatment, with a significant portion (36.4%) of those receiving CAR T-cell therapy affected.

Patients with neurologic AEs incurred an average of $71,982 higher healthcare costs, with CAR T-cell therapy users facing the highest costs, highlighting the financial burden associated with these severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Burden of Neurologic Toxicities Associated with Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States. Broder, MS., Ma, Q., Yan, T., et al.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05963217

NCT05963217 | Study of TBI-2001(Autologous CD19 ... This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05963217?cond=Cancer&aggFilters=funderType%3Aindustry%2CstudyType%3Aint

Study of TBI-2001(Autologous CD19 Specific Chimeric ... One group receives drug A, and the other group receives drug B. So during the trial, participants in one group receive drug A "in parallel" to participants in ...

3. careacross.com careacross.com/clinical-trials/trial/NCT05963217

Study of TBI-2001(Autologous CD19 Specific Chimeric ... This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6511615/

Survival outcomes and efficacy of autologous CD19 ... Purpose: Chimeric Antigen Receptor T(CAR-T) cell therapy is an immunotherapy approach used in treating cancer which has seen rapid development over the ...

5. 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).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7575989/

Efficacy and safety of CD19 chimeric antigen receptor T cells ... The above data suggest that CD19 CAR T product is an effective rescue treatment for relapsed and refractory B-cell lymphoma (20). However, the adverse reactions ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9284423/

CAR T-cell therapy for B-cell lymphoma - PMC - PubMed Central Here, we provide a broad review of the current data on the use of CAR T-cell therapy for B-cell lymphoma and also touch on mechanisms of failure and strategies ...