Iomab-B + CAR-T Cell Therapy for Non-Hodgkin's Lymphoma

Overseen By Silviya Meletath

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: T-cell suppressive therapy

Disqualifiers: Pregnancy, Cardiac conditions, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 30 days post CAR T-cell infusion

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific situation with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Iomab-B + CAR-T Cell Therapy for Non-Hodgkin's Lymphoma?

Research shows that CAR-T cell therapy has been effective in treating certain types of lymphoma, like diffuse large B-cell lymphoma, by using modified immune cells to target cancer. Combining CAR-T cells with radiotherapy may enhance the immune response, potentially improving outcomes for patients. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapy has shown promising results in treating certain types of blood cancers, but it can cause side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). Most patients experience some side effects, but severe cases are less common, and newer versions of the therapy are being developed to improve safety. ^{1 6 7 8 9}

How is the Iomab-B + CAR-T Cell Therapy treatment different from other treatments for Non-Hodgkin's Lymphoma?

Iomab-B + CAR-T Cell Therapy is unique because it combines a radiopharmaceutical (Iomab-B) with CAR-T cell therapy, potentially enhancing the effectiveness of CAR-T cells by using radiation to target and destroy cancer cells, which may improve outcomes compared to CAR-T therapy alone. ^{1 2 3 10 11}

What is the purpose of this trial?

This study is being done to determine the safety, efficacy and tolerability of a single 50 mCi dose of 131I-Apamistamab given prior to CAR-T cell infusion in patients with Relapsed or refractory (R/R) Diffuse large B-cell lymphoma (DLBCL).

Research Team

Farrukh Awan, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for individuals with Diffuse Large B-cell Lymphoma (DLBCL) that has come back or hasn't responded to treatment. Participants should be eligible for CAR-T cell therapy, which is a type of treatment where a patient's immune cells are modified to fight cancer.

Inclusion Criteria

AST and ALT ≤3x upper limit of normal

Total bilirubin ≤1.5x upper limit of normal

I have at least one tumor that shows up on a PET scan.

Exclusion Criteria

Patients with current or prior positive test results for HIV or hepatitis B or C

I do not have any uncontrolled infections.

I have a significant neurological condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

A 6-patient safety run-in to assess safety of 131I-Apamistamab dose prior to CAR-T cell infusion

5-7 days

1 visit (in-person)

Treatment

Participants receive a single 50 mCi dose of 131I-Apamistamab followed by CD19-targeted CAR-T cell therapy

Up to 30 days post CAR T-cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for cytokine release syndrome and neurotoxicity

100 days

Treatment Details

Interventions

• CAR-T cell
• Iomab-B

Trial Overview The study tests the safety and effectiveness of using Iomab-B, a radioactive antibody, before giving CAR-T cell therapy. The goal is to see if this combination can improve outcomes in patients with relapsed or refractory DLBCL.

Participant Groups

Group I: Part B (cohort expansion) Experimental Treatment 2 Interventions

131I-Apamistamab dose will be given 5-7 days prior to a single infusion of CAR-T cell therapy

Group II: Part A (Safety run-in) Experimental Treatment 2 Interventions

131I-Apamistamab dose will be given 5-7 days prior to a single infusion of CD-19 CAR-T cell therapy

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Actinium Pharmaceuticals

Industry Sponsor

Trials

8

Recruited

290+

Findings from Research

The bispecific antibody CD20-TCB is designed to enhance T-cell engagement, which could improve the effectiveness of immunotherapy in treating B-cell lymphoma, particularly in patients with relapsed or refractory non-Hodgkin lymphoma.

Preclinical models have shown promising activity for CD20-TCB, suggesting it may offer a new therapeutic option for patients who have not responded to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. Prakash, A., Diefenbach, CS.[2019]

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

CAR T-cell therapy is an important treatment option for patients with refractory or relapsed diffuse large B-cell lymphoma, providing a targeted approach to combat this aggressive cancer.

The review discusses the criteria for selecting patients for CAR T-cell therapy and emphasizes the importance of bridging therapy and timing to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for the management of refractory/relapsed high-grade B-cell lymphoma: a practical overview. Mohty, M., Dulery, R., Gauthier, J., et al.[2023]

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

Anti-CD19 CAR-modified T cells have demonstrated a 48% overall response rate in treating B-cell malignancies, with complete responses observed in 24% of patients across six phase I clinical trials involving 50 patients.

The study found that conditioning chemotherapy significantly improves progression-free survival (PFS), making it a crucial factor for enhancing the efficacy of CAR T-cell therapy, while the treatment was generally well tolerated with temporary adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Zhu, Y., Tan, Y., Ou, R., et al.[2022]

CAR-T cell therapy shows promising efficacy in treating relapsed/refractory B-cell lymphoma, particularly in older patients and those with specific pathological types, achieving high response and complete remission rates across 17 studies.

While the treatment is generally safe, with most side effects like cytokine-releasing syndrome (CRS) and neurotoxicity being reversible, careful monitoring of these toxicities is essential during clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor-T cells in the treatment of B cell lymphoma: a systematic review and meta-analysis. Zheng, XH., Zhang, XY., Dong, QQ., et al.[2023]

CD4-specific chimeric antigen receptor (CAR) engineered T cells (CD4CART) demonstrated strong cytotoxic effects against CD4+ T cell lymphoma in both laboratory tests and in live mice, indicating their potential as an effective treatment.

The transfer of CD4CART cells significantly reduced tumor growth and improved survival rates in mice with T cell lymphoma compared to control treatments, suggesting a promising therapeutic approach for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma. Cheng, J., Chen, G., Lv, H., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy. [2023]

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

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. [2019]

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

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]

4. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for the management of refractory/relapsed high-grade B-cell lymphoma: a practical overview. [2023]

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

CAR-T Cell Therapy for Lymphoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Anti-CD19 Chimeric Antigen Receptor-T Cell Immunotherapy in Patients With Relapsed/Refractory Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor-T cells in the treatment of B cell lymphoma: a systematic review and meta-analysis. [2023]

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

Constant attack on T cell lymphomas. [2018]

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

CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma. [2022]