ADI-001 for Non-Hodgkin's Lymphoma

(GLEAN-1 Trial)

No longer recruiting at 11 trial locations

Overseen By Adicet Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adicet Therapeutics

Must be taking: Anti CD20 antibody

Disqualifiers: CNS lymphoma, Unrelated malignancy, GvHD, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ADI-001, a type of CAR-T cell therapy, for individuals with Non-Hodgkin's Lymphoma, a cancer affecting the immune system. The study aims to identify the safest and most effective dose of ADI-001 by testing various amounts. It suits those who have tried at least two treatments for B cell malignancies but still have measurable disease. Participants will receive the treatment through an infusion, and researchers will closely monitor the effects to assess its efficacy and safety. As a Phase 1 trial, this research focuses on understanding 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, if you are on treatments like gene therapy or certain cell therapies, you may need to wait a few weeks before joining the study.

Is there any evidence suggesting that ADI-001 is likely to be safe for humans?

Research has shown that ADI-001 was well-tolerated in previous studies. Patients with B cell cancers experienced a good safety profile, with few serious side effects. These studies did not reveal any major safety concerns.

Most participants responded well to the treatment, achieving a 71% overall response rate, meaning many saw their cancer shrink or disappear. This suggests that ADI-001 is both effective and safe for many people.

In summary, earlier studies have demonstrated the treatment's safety, with manageable side effects. This should provide confidence about its safety for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which typically include chemotherapy and targeted therapies, ADI-001 employs a novel approach using engineered T cells. This treatment is unique because it harnesses the power of the body's immune system to specifically target and attack cancer cells. Researchers are particularly excited about ADI-001 because it offers the potential for increased precision in attacking lymphoma cells without harming healthy cells, reducing side effects associated with traditional therapies. Additionally, the infusion method allows for controlled dosing, which can be adjusted to maximize effectiveness while minimizing risks.

What evidence suggests that ADI-001 might be an effective treatment for Non-Hodgkin's Lymphoma?

Research has shown that ADI-001 yields promising results for treating B cell cancers, such as non-Hodgkin's lymphoma. In one study, 71% of patients responded well, with their cancer shrinking. Notably, 63% of patients experienced a complete response, with no detectable cancer. ADI-001 is a type of CAR T-cell therapy that uses specially modified immune cells to target and fight cancer cells. This trial will explore different dosing strategies of ADI-001, including dose escalation, dose extension, and dose expansion, to determine the most effective approach. These findings suggest that ADI-001 could be an effective option for individuals with certain B cell cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Adicet Medical Director

Principal Investigator

Adicet Bio

Are You a Good Fit for This Trial?

Adults with certain B cell malignancies who've had at least two prior treatments, including anti-CD20 antibody therapies. They must have measurable disease, be in good physical condition (ECOG PS of 0 or 1), and not pregnant or breastfeeding. Participants need to use effective birth control and can't join if they've had CNS lymphoma, recent unrelated cancers, gene therapy within six weeks, radiation within four weeks (except palliative), stem cell transplant within six weeks, or allogeneic transplant within three months.

Inclusion Criteria

My B cell cancer has returned or didn't respond to treatment.

I am fully active or can carry out light work.

My blood, kidney, lung, heart, and liver functions are all within normal ranges.

Exclusion Criteria

Opportunistic infections

I am willing to participate in long-term follow-up for safety monitoring.

I have or had lymphoma in my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of ADI-001 to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD)

4 weeks

Multiple visits for dose administration and monitoring

Dose Extension

Participants receive multiple doses of ADI-001 at the MAD/MTD to evaluate safety

4 weeks

Multiple visits for dose administration and monitoring

Dose Expansion

Participants receive ADI-001 at the MTD/MAD to confirm the recommended phase 2 dose

12 months

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• ADI-001

Trial Overview The trial is testing ADI-001 combined with Fludarabine and Cyclophosphamide in patients with various types of B-cell lymphomas. It's a Phase 1 study using a '3+3' design to find the safest dose that also works effectively against the cancer.

How Is the Trial Designed?

Group I: ADI-001 Dose Extension Experimental Treatment 3 Interventions

ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).

Group II: ADI-001 Dose Expansion Experimental Treatment 3 Interventions

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Group III: ADI-001 Dose Escalation Experimental Treatment 3 Interventions

ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).

Who Is Running the Clinical Trial?

Adicet Therapeutics

Lead Sponsor

Trials

4

Recruited

370+

Adicet Bio, Inc

Lead Sponsor

Trials

3

Recruited

310+

Published Research Related to This Trial

In a study of 129 adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) treated with CD19-directed CAR T therapy, 95.4% were hospitalized during treatment, with a median hospital stay of 17 days, highlighting the intensive care required during this therapy.

The estimated 6-month risk of requiring subsequent treatment after CAR T was 36.2%, indicating a significant chance of treatment failure, and emphasizing the need for effective salvage therapies for DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. Jalbert, JJ., Wu, N., Chen, CI., et al.[2022]

CAR T-cell therapy, particularly anti-CD19 CAR T cells, shows strong efficacy in treating resistant forms of B-cell lymphomas, achieving durable complete remissions lasting over 2 years in some patients with refractory diffuse large-B-cell lymphoma (DLBCL).

Despite their effectiveness, CAR T-cell therapies can lead to severe toxicities, such as cytokine-release syndrome and neurological issues, highlighting the need for careful management and ongoing research into safer CAR designs and treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. Brudno, JN., Kochenderfer, JN.[2022]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

Three CAR-T cell therapies (Yescarta®, Kymriah®, and Breyanzi®) have been approved for treating relapsed or refractory diffuse large B cell lymphomas (DLBCL), significantly improving patient outcomes where conventional treatments fail.

Recent updates and real-life data suggest that CAR-T therapies may be effective earlier in treatment and could be extended to other types of B lymphomas, with new CAR-T cell strategies being explored for Hodgkin's and T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR-T cells in lymphomas: Current and evolving role]. Messéant, O., Houot, R.[2021]

Chimeric antigen receptor (CAR) therapy, particularly targeting CD19, has shown significant efficacy in treating patients with chemorefractory B cell malignancies, leading to its potential regulatory approval as a cell-based immunotherapy.

While CAR therapy is effective, it is associated with toxicities such as cytokine release syndrome, neurotoxicity, and B cell aplasia, which require careful management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. Davila, ML., Sadelain, M.[2023]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

In a study of 33 diffuse large B cell lymphoma (DLBCL) patients, low levels of differentiated CD3+CD27-CD28- T cells before CART cell therapy were found to be a strong predictor of overall response and complete remission, suggesting their potential as a biomarker for treatment efficacy.

Despite having similar cytotoxic capabilities, CD3+CD8+ T cells were more effective than CD3+CD4+ T cells in killing CD19+ target cells, highlighting the importance of T cell type in the effectiveness of CART cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency of differentiated CD3+CD27-CD28- T cells predicts response to CART cell therapy in diffuse large B-cell lymphoma. Worel, N., Grabmeier-Pfistershammer, K., Kratzer, B., et al.[2023]

CD19CAR T cells have shown promising results in treating aggressive B-lineage cancers, but their effectiveness can be limited by the loss of the targeted CD19 antigen, leading to treatment failure.

The newly developed adapter CAR T cell technology (AdCAR) allows for multitargeting of different antigens, such as CD20 and CD22, which can enhance the anti-cancer activity and potentially overcome issues related to antigen loss in lymphoma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. Atar, D., Mast, AS., Scheuermann, S., et al.[2022]

Citations

1. investor.adicetbio.com investor.adicetbio.com/news-releases/news-release-details/adicet-bio-reports-positive-data-ongoing-adi-001-phase-1-trial-0

Adicet Bio Reports Positive Data from Ongoing ADI-001 ... ADI-001 demonstrated 71% overall response rate (ORR) and 63% complete response (CR) rate across all dose levels in patients with median 4 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000649712104773X

A Phase 1 Safety and Efficacy Study of ADI-001 Anti-CD20 ... Although autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy is highly effective in R/R B cell NHL, only 40% achieve durable responses.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.7509

A phase 1 study of ADI-001: Anti-CD20 CAR-engineered ... Conclusions: ADI-001 γδ CAR T cells were well tolerated, with a favorable safety profile and encouraging preliminary efficacy. Patients who ...

4. investor.adicetbio.com investor.adicetbio.com/news-releases/news-release-details/adicet-bio-highlights-adi-001-expansion-persistence-and

Adicet Bio Highlights ADI-001 Expansion, Persistence and ... ADI-001 showed robust dose-dependent expansion and persistence in patients with relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma ...

5. sec.gov sec.gov/Archives/edgar/data/1720580/000095017022010791/acet-ex99_1.htm

Adicet Bio Reports Positive Clinical Update from ADI-001 ... Adicet Bio Reports Positive Clinical Update from ADI-001 Phase 1 Trial in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL). As of the February 14, 2022 ASCO ...