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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with relapsed or hard-to-treat diffuse large B-cell lymphoma, a type of blood cancer. It combines a radioactive drug, Iomab-B, with CAR-T cell therapy to evaluate the safety and effectiveness of this combination. The primary goal is to determine if administering Iomab-B before CAR-T cell therapy can improve patient outcomes. Ideal candidates for this trial are those previously treated for this lymphoma but still in need of further assistance. 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 treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Iomab-B, when used before CAR-T cell therapy, is generally safe. In earlier studies, no patients who received Iomab-B died from the treatment within the first 100 days, indicating its safety.

In another study, Iomab-B helped 84% of patients with a different type of cancer achieve complete remission, meaning their cancer was no longer detectable. This suggests that most patients handle the treatment well.

CAR-T cell therapy, the other part of this treatment combination, has been used in patients with non-Hodgkin's lymphoma and has led to significant improvements. While some side effects are common, patients generally tolerate this therapy well.

Overall, studies indicate that both Iomab-B and CAR-T cell therapy are generally safe and well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Iomab-B combined with CAR-T cell therapy for Non-Hodgkin's Lymphoma because it offers a unique approach compared to current treatments like chemotherapy and radiation. Iomab-B uses a targeted radioimmunotherapy approach with 131I-Apamistamab, which helps deliver radiation directly to cancer cells, potentially reducing damage to healthy cells. Additionally, the incorporation of CAR-T cell therapy, which involves engineering a patient’s own immune cells to better attack cancer cells, represents a personalized and potentially more effective treatment strategy. This combined approach could offer a powerful one-two punch against cancer, targeting it more precisely and harnessing the body's immune system for a stronger response.

What evidence suggests that Iomab-B + CAR-T cell therapy could be effective for Non-Hodgkin's Lymphoma?

In this trial, participants will receive a combination of Iomab-B and CAR-T cell therapy. Studies have shown that Iomab-B, which uses a radioactive substance called iodine-131 apamistamab, effectively treats certain blood cancers. In some studies, up to 84% of patients with a type of leukemia achieved complete remission, meaning the cancer was no longer detectable, after receiving Iomab-B. Research indicates that CAR-T cell therapy is effective for Non-Hodgkin's Lymphoma, with many patients experiencing improved quality of life. Clinical data supports that CAR-T therapy can lead to remission in patients with hard-to-treat lymphomas. Together, these treatments aim to help the immune system fight cancer more effectively. ^{5 6 7 8 9}

Who Is on the Research Team?

Farrukh Awan, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8261235/

A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin ... Approval was based on an experiment in which 166 patients with indolent NHL received Rituximab and ultimately had a complete remission (CR) rate of 6% and an ...

2. astctjournal.org astctjournal.org/article/S2666-6367(25)01462-9/fulltext

Patient-Reported Outcomes of CAR T-Cell Therapy in Non- ... This study demonstrates that CAR T-cell therapy improves overall HRQoL in NHL patients across different countries in the real-world setting.

3. ashpublications.org ashpublications.org/bloodadvances/article/9/21/5571/546741/Comparative-real-world-outcomes-of-CD19-directed

Comparative real-world outcomes of CD19-directed CAR T ... The primary safety outcomes were the incidence and severity of cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), ...

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

Safety and efficacy of autologous humanized CD19 CAR-T ... The median peak proportion of CD19 CAR-T cell proliferation was 44.38% (range, 7.06–83.00%). The median peak number of circulating CD19 CAR-T ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00070-7/fulltext

Treatment of non-Hodgkin lymphoma with point-of-care ... After a median duration of follow up from CAR T-cell infusion of 24.5 months (IQR 17–32) among the event-free, 7 patients relapsed and 10 died.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06768905

NCT06768905 | Study of IOMAB-ACT Followed by CAR-T ... 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 ...

7. ir.actiniumpharma.com ir.actiniumpharma.com/press-releases/detail/306/actinium-pharmaceuticals-highlights-analysis-of-pivotal

Actinium Pharmaceuticals Highlights Analysis of Pivotal ... Key highlights include near universal engraftment and no 100-day non-relapse mortality in patients randomized to Iomab-B arm; ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04512716

NCT04512716 | Iomab-ACT: A Pilot Study of 131-I ... This is a pilot study; patients will receive 131-I apamistamab prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I ...

9. onclive.com onclive.com/view/conditioning-therapy-with-iomabb-leads-to-high-transplant-rate-in-active-aml

Conditioning Therapy With Iomab-B Leads to High ... Iodine (131I) apamistamab (Iomab-B) conditioning induced a complete remission in 84% (31/38) of patients with active acute myeloid leukemia, ...