ATA3219 for Non-Hodgkin's Lymphoma

No longer recruiting at 6 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Atara Biotherapeutics

Must not be taking: Immunosuppressants, Corticosteroids

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ATA3219, a type of CAR T-cell therapy, for individuals with B-cell non-Hodgkin's lymphoma, a blood cancer that has returned or resisted treatment. The main goal is to determine the treatment's safety and effectiveness. Researchers are testing four different dose levels to identify the most effective and safest one. This trial may suit those who have tried at least two other treatments for their lymphoma but still have the disease. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that ATA3219 is likely to be safe for humans?

Research shows that treatments like ATA3219 have been safe for people with non-Hodgkin's Lymphoma. These treatments use specially designed immune cells and have undergone previous testing, with most participants tolerating them well. Although some side effects occurred, they were manageable. Since ATA3219 remains in the early stages of testing, researchers continue to learn about its safety. Participants should understand that early trials primarily focus on assessing the treatment's safety and side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ATA3219 for treating Non-Hodgkin's Lymphoma because it offers a fresh approach compared to traditional therapies like chemotherapy, radiation, and targeted therapies such as monoclonal antibodies. Unlike these standard treatments, ATA3219 is a novel therapy administered as a single IV infusion, which could potentially simplify and streamline the treatment process. Its unique composition and dosing levels aim to effectively target lymphoma cells with possibly fewer side effects. This innovative mechanism of action has the potential to improve patient outcomes and enhance quality of life, making it a promising option in the fight against this type of cancer.

What evidence suggests that ATA3219 might be an effective treatment for non-Hodgkin's lymphoma?

Research is investigating ATA3219 as a potential treatment for relapsed or refractory B-cell non-Hodgkin's Lymphoma (NHL). The trial will test different dose levels of ATA3219, with participants receiving a single IV infusion of one dose level on Day 1. This treatment uses pre-made immune cells specially modified to target and attack cancer cells. Although detailed results from the studies are not yet available, early findings suggest this method could be promising for difficult NHL cases. CAR T-cell therapy, the type of treatment under study, has proven effective in treating similar conditions, offering hope for its success in NHL as well. More detailed results are expected soon to provide clearer evidence. ^{1 3 4 6 7}

Who Is on the Research Team?

Aditi Mehta, DO

Principal Investigator

Atara Biotherapeutics

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ATA3219

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).

How Is the Trial Designed?

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+

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. atarabio.com atarabio.com/pipeline/ata3219/

ATA3219: Off-the-Shelf Allogeneic CD19 Program ... ATA3219 is currently being investigated in a Phase 1 trial for subjects with relapsed/refractory B-cell Non-Hodgkin's Lymphoma. Initial clinical data ...

2. atarabio.com atarabio.com/patients-families/nhl-ata3219-trial/

NHL ATA3219 trial A study to evaluate the safety and preliminary efficacy of ATA3219 in participants with relapsed/refractory B-cell non-Hodgkin lymphoma. ClinicalTrials.gov ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT06256484

ATA3219-NHL-103 / NCT06256484 Study designed to evaluate safety, preliminary efficacy, pharmacokinetics, and biomarkers; Initial clinical data anticipated in Q1 2025.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11269961/

“Off-The-Shelf” allogeneic chimeric antigen receptor T-cell ... “Off-the-shelf” allogeneic CAR T-cell therapy (alloCAR T) has emerged as a promising alternative therapy, albeit experimental to date.

5. firstwordpharma.com firstwordpharma.com/story/5855374

Atara Biotherapeutics Announces First Quarter 2024 ... Enrolling ATA3219 Non-Hodgkin's Lymphoma Study, with Initial Clinical Data Expected in Q4 2024 ... The data demonstrate that ATA3219 CAR T ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324924006571

ALLOGENEIC CD19 CAR EBV T CELLS FOR THE ... In support of this, CD19 CAR EBV T cells have previously demonstrated a favorable safety profile in non-Hodgkin's Lymphoma [Curran KJ 2020]. Methods ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06256484

NCT06256484 | A Study to Evaluate the Safety and ... 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 ...