ATA3219 for Non-Hodgkin's Lymphoma

Recruiting at 6 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Atara Biotherapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HIV, Hepatitis B/C, CNS pathology, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and preliminary efficacy of ATA3219 in participants with relapsed/refractory (R/R) B-cell non-Hodgkin Lymphoma (NHL).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, certain therapies like corticosteroids, chemotherapeutic agents, and investigational drugs are not allowed before the conditioning regimen, so you may need to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment ATA3219 for Non-Hodgkin's Lymphoma?

Research shows that CD19-targeted CAR-T cells, similar to ATA3219, have been effective in treating B-cell malignancies, including Non-Hodgkin's Lymphoma, with a high complete response rate. These treatments have shown promise in patients with relapsed or refractory conditions, indicating potential effectiveness for ATA3219. ^{1 2 3 4 5}

What is known about the safety of ATA3219 (CD19 CAR T-cell therapy) in humans?

CD19 CAR T-cell therapy, which includes treatments like ATA3219, has been studied for safety in various trials. Common side effects include cytokine release syndrome (a reaction causing fever and inflammation) and neurotoxicity (nerve damage), but these are often manageable with care. Some studies report no serious adverse events directly linked to the treatment, indicating it can be safe when administered properly. ^{6 7 8 9 10}

What makes the treatment ATA3219 unique for non-Hodgkin's lymphoma?

ATA3219 is a type of CAR T-cell therapy that targets the CD19 protein on B-cells, similar to other CAR T-cell treatments, but it is unique because it uses EBV (Epstein-Barr Virus) to enhance the T-cells' ability to fight cancer. This approach may offer a novel way to treat patients who have not responded to other therapies. ^{11 12 13 14 15}

Research Team

Aditi Mehta, DO

Principal Investigator

Atara Biotherapeutics

Eligibility Criteria

This trial is for people with B-cell non-Hodgkin Lymphoma that has come back or didn't respond to previous treatments. Specific details on eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions.

Inclusion Criteria

I can stay near the clinic for 28 days after each treatment.

My condition didn't improve after 2 treatments; if I had a cell transplant, my disease returned within a year.

Written informed consent as per protocol

Exclusion Criteria

I am currently pregnant or breastfeeding.

I am on medication for an autoimmune disorder or inflammation.

I have a history of HIV or hepatitis B or C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy within 7 days of enrollment before administration of ATA3219

1 week

Treatment

Participants receive ATA3219 via IV infusion and are hospitalized for at least 1 week for safety monitoring

1 week

1 visit (in-person)

Dose Limiting Toxicity Observation

Participants are observed for dose-limiting toxicity over a 28-day period

4 weeks

Follow-up

Participants are monitored for response and safety for up to 24 months from the last dose of ATA3219

24 months

Long-term Follow-up

A separate long-term follow-up study will be conducted to follow participants for up to a total of 15 years

15 years

Treatment Details

Interventions

• ATA3219 (CAR T-cell Therapy)

Trial Overview The study is testing ATA3219's safety and how well it works in treating various types of B-cell non-Hodgkin Lymphoma that have relapsed or are refractory (resistant to treatment).

Participant Groups

Group I: ATA3219 Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive a single IV infusion of ATA3219 Dose Level 4 on Day 1.

Group II: ATA3219 Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive a single IV infusion of ATA3219 Dose Level 3 on Day 1.

Group III: ATA3219 Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive a single IV infusion of ATA3219 Dose Level 2 on Day 1.

Group IV: ATA3219 Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive a single IV infusion of ATA3219 Dose Level 1 on Day 1.

Who Is Running the Clinical Trial?

Atara Biotherapeutics

Lead Sponsor

Trials

14

Recruited

740+

Findings from Research

A patient with primary mediastinal large B-cell lymphoma achieved a complete metabolic response after receiving pembrolizumab following relapse 3.5 months post-CD19-directed CAR T-cell therapy, indicating the potential efficacy of immune checkpoint inhibitors in this setting.

Despite achieving remission, treatment with pembrolizumab was stopped after six cycles due to pneumonitis, highlighting the importance of monitoring for side effects while using immune checkpoint inhibitors after CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review. Dimou, M., Bitsani, A., Bethge, W., et al.[2022]

A novel CAR T-cell therapy targeting CD79b has been developed, showing strong antitumor activity against B-cell lymphomas in both laboratory and animal models, including the ability to attack tumors that have relapsed after CD19-targeted therapies.

The CD79b CAR T cells demonstrated effective proliferation and cytotoxic activity without significant signs of exhaustion, supporting their potential for use in a phase 1 clinical trial for patients with relapsed or refractory B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas. Chu, F., Cao, J., Liu, J., et al.[2023]

Adoptive T cell therapy using anti-CD19-CAR5-T cells, which secrete anti-PD-L1, showed improved effectiveness in killing aggressive B cell lymphomas compared to traditional anti-CD19-CAR-T cells, especially at low effector-to-target ratios.

The study demonstrated that anti-CD19-CAR5-T cells not only proliferated better but also enhanced cytotoxicity against CD19+/PD-L1high tumor cells, suggesting a promising new approach for treating difficult-to-treat B cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T cells secreting anti-PD-L1 single-chain variable fragment attenuate PD-L1 mediated T cell inhibition. Yuti, P., Wutti-In, Y., Sawasdee, N., et al.[2022]

In a study involving 9 patients with relapsed or refractory B cell non-Hodgkin's lymphoma, both CD28 and 4-1BB targeted CAR-T cells showed similar antitumor efficacy, achieving a complete response rate of 67% within 3 months.

However, the 4-1BB (BBz CAR-T) cells were better tolerated, with only mild adverse events, while the CD28 (28z CAR-T) cells caused severe side effects, leading to the discontinuation of further evaluation for that group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin's Lymphoma. Ying, Z., He, T., Wang, X., et al.[2020]

CD19 is a highly effective target for CAR T-cell therapies, showing significant responses in patients with relapsed B-cell malignancies, particularly chronic lymphocytic leukemia and acute lymphoblastic leukemia.

While treatment with CD19-CAR T cells can lead to severe systemic inflammatory reactions, these are generally reversible with proper medical care, highlighting the importance of monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR trials. Ramos, CA., Savoldo, B., Dotti, G.[2022]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

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]

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has become a significant advancement in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), with two such therapies approved by regulatory agencies.

Despite the success of CD19-targeting CAR T-cells, some patients still experience relapses, highlighting the need for ongoing research into resistance mechanisms and potential strategies to overcome them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia. Saleh, K., Pasquier, F., Bigenwald, C., et al.[2023]

CD37CAR T cells have shown comparable efficacy to CD19CAR T cells in controlling tumor growth in both in vitro and in vivo models, making them a promising alternative for treating B-cell lymphomas.

Unlike CD19CAR T cells, CD37CAR T cells effectively target tumors that have lost CD19 expression, demonstrating their potential to overcome resistance in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma. Köksal, H., Dillard, P., Josefsson, SE., et al.[2020]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

The study involved 93 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL), showing that CAR-T cells produced from ALL patients expanded better and had a higher frequency of CAR-T cells compared to those from NHL patients.

The overall response rate to CAR-T cell therapy was high, with 84% in ALL patients and 62% in NHL patients, indicating that in-house production of CAR-T cells is efficient and effective, achieving target doses for nearly all patients within 9 to 10 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients. Itzhaki, O., Jacoby, E., Nissani, A., et al.[2020]

CD19 CAR-T cells have shown significant promise in treating relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), indicating a major advancement in therapy for this condition.

The study highlights the safety and effectiveness of using CAR-T cells derived from naïve, stem, and central memory T cells in adults, suggesting that these cell types may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing CD19 Chimeric Antigen Receptor T Cells Through Memory-Enriched T Cells. El Marabti, E., Abdel-Wahab, O.[2023]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T cells secreting anti-PD-L1 single-chain variable fragment attenuate PD-L1 mediated T cell inhibition. [2022]

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

Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin's Lymphoma. [2020]

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

CD19-CAR trials. [2022]

6. England pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). [2020]

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

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

9. 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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia. [2023]

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

Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma. [2020]

12. Germany pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients. [2020]

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

Enhancing CD19 Chimeric Antigen Receptor T Cells Through Memory-Enriched T Cells. [2023]

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

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]