CAR T-Cell Therapy for Lymphoma

(MAGENTA Trial)

Recruiting at 1 trial location

Overseen By Rayne H. Rouce

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, Immunosuppressive treatment

Disqualifiers: Active infection, HIV, Other cancer, others

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

Compensation: Varies

Number of Visits: 7

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating lymphoma, a cancer affecting the lymph glands, using a special type of white blood cell called T cells. Researchers combine T cells with an antibody, a protein targeting cancer cells, to create a stronger treatment. The study focuses on patients who have relapsed after a bone marrow transplant and have T-cell leukemia or lymphoma. It specifically seeks those whose cancer returned after a transplant and who still have a donor available for additional T cells. Participants will help test whether this combined treatment can last longer in the body and fight cancer more effectively. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving any investigational agents or have received tumor vaccines within the previous 6 weeks. Also, if you are taking corticosteroids for GVHD at a dose greater than 0.5mg/kg prednisone equivalent, you may not be eligible.

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

Research has shown that autologous CD5.CAR/28zeta CAR T cells are safe for patients with T-cell lymphomas. Studies have found that these cells can trigger positive responses without causing serious side effects. They specifically target and attack cancer cells, helping to protect healthy cells.

For allogeneic CD5.CAR/28zeta CAR T cells, which use donor T cells, safety information is still being collected. This treatment resembles the autologous version, and the current trial phase focuses on ensuring its safety. Researchers are monitoring early results to confirm the treatment is well-tolerated.

In both cases, while these treatments are still under investigation, early findings suggest that serious side effects are rare. As research continues, more safety information will become available to support these initial findings. Prospective participants should always discuss with their healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these CAR T-cell therapies for lymphoma because they harness the power of the immune system in a novel way. Unlike traditional treatments like chemotherapy and radiation, which can indiscriminately target both healthy and cancerous cells, these therapies use genetically engineered T cells to specifically target and destroy lymphoma cells. The key feature here is that the T cells are modified to express a chimeric antigen receptor (CAR) that specifically binds to the CD5 protein found on the surface of lymphoma cells. This targeted approach could potentially lead to more effective treatments with fewer side effects, which is a significant advancement over current options.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Studies have shown that CAR T-cell therapy with special CD5 receptors and CD28 can lead to strong responses in patients with T-cell leukemia or lymphoma. In this trial, participants will receive either autologous CD5.CAR/28zeta CAR T cells or allogeneic CD5.CAR/28zeta CAR T cells. Research indicates that these CD5-specific CAR T-cells effectively target and destroy cancer cells with the CD5 marker on their surface. Previous findings suggest that these treatments can significantly reduce cancer, allowing some patients to proceed to further bone marrow transplants for better outcomes. Overall, this approach has shown promise in providing a strong attack against these difficult-to-treat cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Rayne H. Rouce

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for people under 75 with certain T-cell blood cancers who haven't responded to other treatments. They should have a life expectancy over 12 weeks, be at least two months post-transplant if applicable, and not currently on certain medications or have severe active infections.

Inclusion Criteria

I am a candidate for a stem cell transplant and have a confirmed donor.

My tumor is CD5 positive with more than half of the cells being CD5 positive.

I have a donor for EBV-specific T cell treatment.

Exclusion Criteria

I do not have an active significant viral infection.

I have a central nervous system disorder or autoimmune disease affecting my brain.

I am currently taking antibiotics for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-treatment Chemotherapy

Participants receive cyclophosphamide and fludarabine to decrease T cell numbers before infusion

1 week

3 visits (in-person)

T-Cell Infusion

Participants receive an infusion of CD5.CD28 Chimeric Receptor T cells

1 day

1 visit (in-person)

Initial Monitoring

Participants are monitored for side effects and viral infections post-infusion

6-8 weeks

At least 2 visits per week (in-person)

Follow-up

Participants are monitored for long-term safety and effectiveness of gene transfer

15 years

Regular visits as per schedule

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic CD5.CAR/28zeta CAR T cells
• Autologous CD5.CAR/28zeta CAR T cells
• Cytoxan
• Fludarabine
• Rituximab

Trial Overview The study tests modified T-cells with a special receptor (CD5.CAR/28zeta) designed to target cancer cells in patients with specific types of T-cell leukemia or lymphoma. It's seeing how well these engineered T-cells work and how long they last in the body.

How Is the Trial Designed?

Group I: Autologous CD5.CAR/28zeta CAR T cells (Group A) - NOW CLOSED Experimental Treatment 1 Intervention

Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.If patients have experienced either a partial response or stable disease and completed the 6 week toxicity evaluation without evidence of DLT or other infectious complications, they will be eligible to receive up to 3 additional infusions of CD5 CAR.T cells. Patients remain eligible for up to 3 additional infusions as long as they continue to have a clinical response and absence of safety concerns. If patients experience a complete response following an additional infusion, investigators will recommend they proceed to allogeneic HSCT. Once dose escalation is completed, the trial will be expanded and treat up to an additional 6 patients (2 cohorts) at the MTD in each group to gather additional safety data and preliminary efficacy data.

Group II: Allogeneic CD5.CAR/28zeta CAR T cells (Group B) Experimental Treatment 1 Intervention

Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.If patients have experienced either a partial response or stable disease and completed the 6 week toxicity evaluation without evidence of DLT or other infectious complications, they will be eligible to receive up to 3 additional infusions of CD5 CAR.T cells. Patients remain eligible for up to 3 additional infusions as long as they continue to have a clinical response and absence of safety concerns. If patients experience a complete response following an additional infusion, investigators will recommend they proceed to allogeneic HSCT. Once dose escalation is completed, the trial will be expanded and treat up to an additional 6 patients (2 cohorts) at the MTD in each group to gather additional safety data and preliminary efficacy data.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

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]

Allogeneic CAR-T cells targeting CD19 have shown effective treatment outcomes in children and young adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), achieving complete remission in all patients studied, with a median follow-up of 12 months.

The safety profile of these donor-derived CAR-T cells was comparable to that of autologous CAR-T cells, with manageable side effects such as mild cytokine release syndrome and low-grade neurotoxicity, indicating a promising alternative for patients unable to access autologous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic, donor-derived, second-generation, CD19-directed CAR-T cells for the treatment of pediatric relapsed/refractory BCP-ALL. Del Bufalo, F., Becilli, M., Rosignoli, C., et al.[2023]

Gene-modified T cells expressing a CD19-specific chimeric antigen receptor (CAR) effectively targeted and eliminated B cell lymphoma cells in mice, demonstrating strong antitumor activity even in the presence of normal CD19-positive B cells.

Despite the initial success in eradicating tumors, the CAR T cells showed a significant decrease in numbers over time, but importantly, there were no signs of harmful effects on normal tissues, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural expression of the CD19 antigen impacts the long-term engraftment but not antitumor activity of CD19-specific engineered T cells. Cheadle, EJ., Hawkins, RE., Batha, H., et al.[2023]

A new CAR T cell therapy targeting CD79b has been developed, which shows effective recognition and destruction of B-cell lymphoma cells, including those that have lost CD19 expression, addressing a common issue of disease relapse.

The study demonstrated that CAR T cells targeting CD79b can work alone or in combination with CD19 targeting, providing a promising strategy to prevent antigen escape in B-cell lymphomas, based on experiments with cell lines and patient-derived models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19. Ormhøj, M., Scarfò, I., Cabral, ML., et al.[2020]

CAR-T cell therapy has shown effectiveness in treating various types of blood cancers, including diffuse large B-cell lymphoma and mantle cell lymphoma, by targeting the CD19 antigen.

The study compares CAR-T cell therapy and allogeneic stem cell transplantation (ALLO-SCT) to determine the best scenarios for using each treatment, highlighting their shared immune mechanisms but differing characteristics in treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy. Castagna, L., Bono, R., Tringali, S., et al.[2022]

In a study involving 8 patients with B cell lymphoma who had previously undergone allogeneic stem cell transplants, CD19-directed CAR T cell therapy showed a promising response rate of 75%, indicating its efficacy in this challenging patient population.

The treatment was generally well tolerated, with only one instance of severe cytokine release syndrome and neurotoxicity; however, prolonged grade ≥ 3 cytopenia was observed in patients receiving the commercially manufactured axi-cel, highlighting a potential safety concern that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of CD19 Chimeric Antigen Receptor T Cell Treatment for B Cell Lymphoma Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Schubert, ML., Dietrich, S., Stilgenbauer, S., et al.[2021]

In a phase I trial involving 10 patients with T-cell acute lymphoblastic leukemia (ALL) and lymphoma, both autologous and allogeneic anti-CD7 CAR-T therapies were tested, showing no dose-limiting toxicity and a manageable safety profile with cytokine release syndrome occurring in some patients.

Allogeneic CAR-T cells resulted in higher remission rates and more durable CAR-T survival compared to autologous CAR-T cells, suggesting that allogeneic therapy may be a more effective treatment option for T-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies. Zhang, Y., Li, C., Du, M., et al.[2023]

In a study involving five adults with relapsed B cell acute lymphoblastic leukemia (B-ALL), treatment with autologous T cells modified to express a CD19-specific CAR (19-28z) led to rapid tumor eradication and complete remissions without minimal residual disease (MRD), indicating strong efficacy of this therapy.

The treatment was generally well tolerated, although patients with higher tumor burdens experienced significant cytokine elevations, which required management with steroids, highlighting the need for monitoring and potential intervention during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Brentjens, RJ., Davila, ML., Riviere, I., et al.[2023]

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 becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03081910

Study Details | NCT03081910 | Autologous T-Cells ... In this study investigators will attach the CD5 chimeric receptor with CD28 added to it to the patient's T cells or the previous bone marrow transplant donor's ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9776964/

Harnessing the Potential of Chimeric Antigen Receptor T- ... The study showed CR at 30 days in 18 out of 20 (90%) patients, allowing 37% of responders to proceed to HSCT. Of the 12 patients who did not ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39354195/

Allogeneic CD5-specific CAR-T therapy for relapsed/ ... These results suggest this CD5-specific CAR-T intervention has a high remission rate for T-ALL patients. Evidence also suggests the risk of late-onset severe ...

4. withpower.com withpower.com/trial/phase-1-lymphoma-non-hodgkin-10-2017-62db0

CAR T-Cell Therapy for Lymphoma (MAGENTA Trial) Allogeneic CAR-T cells resulted in higher remission rates and more durable CAR-T survival compared to autologous CAR-T cells, suggesting that allogeneic therapy ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)01477-0/fulltext

Under the Hood: Evidence-Based Review of Allogeneic ... Autologous CAR-T therapies have shown remarkable efficacy but face multiple challenges, including the need to collect autologous T cell ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-00726

CD5.CAR/28 T Cells, Cyclophosphamide, and Fludarabine ... This phase I trial studies the side effects and best dose of autologous (derived from cells collected from the patient) or allogeneic (derived from previous ...

7. targetedonc.com targetedonc.com/view/fda-grants-orphan-drug-designation-to-mb-105-for-r-r-t-cell-lymphoma

FDA Grants Orphan Drug Designation to MB-105 for R/R ... MB-105, a first-in-class CD5-targeted CAR T-cell therapy, received FDA orphan drug designation for relapsed/refractory T-cell lymphoma.