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

42 Participants Needed

Trial Summary

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.

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

Research on similar CAR T-cell therapies, like those targeting CD19, shows they can be effective in treating certain blood cancers, achieving high remission rates in patients with relapsed or refractory conditions. Additionally, studies on anti-CD7 CAR-T cells in T-cell malignancies have shown promising results, with high remission rates and manageable side effects, suggesting potential effectiveness for similar CAR T-cell therapies. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy has been generally well tolerated in clinical trials, with some patients experiencing mild to moderate side effects like cytokine release syndrome (a condition where the immune system is overly activated) and neurotoxicity (nerve damage). These side effects were usually manageable, and the therapy showed promising safety profiles in both pediatric and adult patients with different types of leukemia and lymphoma. ^{1 2 4 6 7}

What makes the CD5 CAR T-cell treatment for lymphoma unique?

The CD5 CAR T-cell treatment is unique because it uses genetically engineered T-cells to specifically target and attack lymphoma cells, and it can be derived from either the patient's own cells (autologous) or a donor's cells (allogeneic). This approach is different from traditional treatments as it offers a personalized and potentially more effective option for patients with relapsed or refractory lymphoma. ^{2 8 9 10 11}

What is the purpose of this trial?

Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma (lymph gland cancer). The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research combines two different ways of fighting disease, antibodies and T cells. Antibodies are proteins that protect the body from bacterial and other diseases. T cells, or T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have shown promise treating patients with cancers, but have not been strong enough to cure most patients. T lymphocytes can kill tumor cells but there normally are not enough of them. Some researchers have taken T cells from a person's blood, grown more in the lab then given them back to the person. In some patients who've had recent bone marrow or stem cell transplant, the number of T cells in their blood may not be enough to grow in the lab. In this case, T cells may be collected from their previous transplant donor, who has a similar tissue type. The antibody used in this study, called anti-CD5, first came from mice that have developed immunity to human leukemia. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5. CD5 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD5 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. In the lab, investigators have also found that T cells work better if stimulating proteins, such as one called CD28, are also added. Adding the CD28 makes the cells grow better and last longer in the body, giving them a better chance of killing the leukemia or lymphoma 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 T cells. The investigators will then test how long the cells last. The decision to use the bone marrow transplant donor's T cells instead of the patient's will be based on 1) whether there is an available and willing donor and 2) the likelihood of the patient's T cells being able to grow in the lab. These CD5 chimeric receptor T cells with CD28 are investigational products not approved by the FDA.

Research Team

Rayne H. Rouce

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Autologous CD5.CAR/28zeta CAR T cells (Group A) 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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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. United States 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. [2022]

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

Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies. [2023]

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

Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19. [2020]

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

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. [2023]

5. United States 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. [2021]

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

Allogeneic, donor-derived, second-generation, CD19-directed CAR-T cells for the treatment of pediatric relapsed/refractory BCP-ALL. [2023]

7. United States 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. [2023]

8. 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]

9. Switzerland 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. [2022]

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

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. [2023]

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

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