19 Participants Needed

CAR-T Therapy for B-Cell Lymphoma

MB
Overseen ByMarcus Butler, M.D.
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial tests TBI-2001, a therapy that modifies a patient's immune cells to better attack cancer. It targets patients whose cancers have not responded to other treatments. The treatment works by enhancing the immune cells' ability to kill cancer cells.

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.

What data supports the effectiveness of the treatment CAR-T Therapy for B-Cell Lymphoma?

Research shows that CAR T-cells targeting CD19 have been effective in treating B-cell lymphomas, with some patients experiencing significant tumor regression and prolonged elimination of B-lineage cells. This suggests that CAR-T therapy is a promising approach for treating B-cell malignancies.12345

Is CAR-T therapy for B-cell lymphoma safe?

CAR-T therapy for B-cell lymphoma can cause serious side effects, including neurologic issues and cytokine release syndrome (a severe immune reaction). However, some studies have shown it to be generally safe, with manageable side effects, in certain patient groups.16789

How is the treatment TBI-2001 unique for B-cell lymphoma?

TBI-2001 is a type of CAR T-cell therapy, which uses a patient's own T-cells (a type of immune cell) that are modified to better recognize and attack B-cell lymphoma cells by targeting the CD19 protein on their surface. This approach is different from traditional treatments because it involves engineering the patient's immune cells to fight the cancer, offering a new option for those with relapsed or refractory B-cell lymphoma.1371011

Research Team

Marcus Butler | Immunology

Marcus Butler

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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
See 6 more

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.
See 13 more

Timeline

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

Treatment Details

Interventions

  • Cyclophosphamide
  • Fludarabine
  • TBI-2001
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Experimental: Dose Level 1 to 3Experimental Treatment3 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.

Find a Clinic Near You

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+

Findings from Research

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

References

Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells. [2023]
CARs and cancers: questions and answers. [2021]
T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]
Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. [2023]
Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. [2021]
Economic Burden of Neurologic Toxicities Associated with Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States. [2022]
Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. [2023]
CD19 CAR-T Cell Therapy Induced Immunotherapy Associated Interstitial Pneumonitis: A Case Report. [2022]
Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
CD19-directed CAR T-cell therapy in B-cell NHL. [2021]