Memory-Enriched T Cells for Non-Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: Uncontrolled illness, Active infections, Brain metastases, others

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

Compensation: Varies

Number of Visits: 20

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with B-cell non-Hodgkin lymphoma that has recurred after other treatments. It uses genetically modified T cells, a type of immune cell from the patient's own body, to kill cancer cells and prevent recurrence. The trial includes two groups, each receiving a slightly different version of these modified T cells: Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells and Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes. Suitable candidates for this trial are those previously treated for B-cell non-Hodgkin lymphoma, such as diffuse large B-cell lymphoma or mantle cell lymphoma, whose cancer has returned. As a Phase 1 trial, the 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 does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational drugs, certain doses of corticosteroids, or if you have an active autoimmune disease requiring systemic treatment.

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

A previous study found that TCM-derived CD19 CAR T-cell therapy was safe for patients with non-Hodgkin lymphoma undergoing stem cell transplants. These T cells are modified in a lab to enhance their ability to attack cancer cells. Researchers observed that most patients tolerated the treatment well, experiencing no severe side effects.

Another study examined TN/MEM-enriched T cells, also modified to combat lymphoma. This study focused on side effects and determining optimal doses. Early results suggest these cells are safe for use after chemotherapy in patients with non-Hodgkin lymphoma, with side effects typically mild and manageable.

As this trial is in its early stages, the primary goal is to identify the highest safe dose. The treatment is still under safety evaluation, requiring further information. However, the studies so far provide promising insights into its safety for potential participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Non-Hodgkin's Lymphoma because they use engineered T cells to specifically target cancer cells. Unlike traditional chemotherapy or radiation, which can harm healthy cells, these T cells are modified to home in on cancer cells by expressing a specific protein, CD19CAR. The treatments also involve enriching these T cells with memory-like features (TCM and TN/MEM), which may enhance their ability to remember and attack cancer cells more effectively. This precision and potential for long-term cancer cell targeting make these treatments a promising new avenue for combating Non-Hodgkin's Lymphoma.

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

Research has shown that specially modified T cells can help treat B-cell non-Hodgkin lymphoma, particularly in patients whose cancer has returned. In this trial, participants will receive one of two types of T cells following a stem cell transplant. These T cells are designed to find and attack cancer cells by targeting a specific marker called CD19 on the surface of lymphoma cells. Participants in Arm 1 will receive TCM-enriched T cells, which studies indicate are safe and promising for patients at high risk of poor outcomes. Participants in Arm 2 will receive TN/MEM-enriched T-lymphocytes, which early trials have shown to be safe and effective for related conditions. Overall, these therapies offer hope by boosting the body's ability to fight cancer cells that remain after standard treatments. ^{2 3 4 5 6}

Who Is on the Research Team?

Elizabeth Budde, MD, PhD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent B-cell non-Hodgkin lymphoma who are eligible for a stem cell transplant. They must have a life expectancy of at least 16 weeks, not require oxygen support, and have good organ function. Pregnant women or those on corticosteroids/immunosuppressives can't join. Participants need to agree to use contraception during the study.

Inclusion Criteria

I have a type of aggressive B-cell lymphoma and need a stem cell transplant due to recurrence or high-risk disease.

My B-cell NHL diagnosis is confirmed to be intermediate or high grade.

I had a stem cell transplant without disease progression after my last treatment.

Exclusion Criteria

I have no active cancer except for my current diagnosis, or any past cancer is in complete remission.

I am on medication to suppress my immune system due to an autoimmune disease.

I don't have any health issues that would prevent me from undergoing a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing T cells following HSCT

28 days

Day 2 or 3 post-HSCT

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Within 18-24 hours, then 18-72 hours, weekly for 1 month, monthly for 1 year, at 18, 24, and 36 months, and then annually

Optional Second T Cell Infusion

Patients who experience disease progression and have not experienced serious treatment-related toxicities may receive an optional second T cell infusion

What Are the Treatments Tested in This Trial?

Interventions

• Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells
• Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes

Trial Overview The trial tests genetically modified T cells made from the patient's own immune cells after a stem cell transplant. These 'memory enriched' T cells are designed to recognize and kill lymphoma cells that survived the transplant, potentially preventing cancer recurrence.

How Is the Trial Designed?

Group I: Arm 2 (autologous TN/MEM-enriched T cells) Experimental Treatment 2 Interventions

Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT.

Group II: Arm 1 (autologous TCM-enriched T cells) Experimental Treatment 2 Interventions

Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TCM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I clinical trial involving 10 patients with relapsed/refractory non-Hodgkin lymphoma, the engineered T cells expressing a bispecific CAR targeting CD19 and CD20 demonstrated a high overall response rate of 90%, with 70% achieving complete remission.

The treatment was found to be safe, with no cases of neurotoxicity and only one instance of dose-limiting toxicity, indicating that CART19/20 T cells can provide effective therapy with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma. Larson, SM., Walthers, CM., Ji, B., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

The study developed a novel CD30-chimeric antigen receptor (CAR) T cell therapy using memory stem T cells (TSCM), which showed improved persistence and antitumor activity against Hodgkin lymphoma in mouse models.

CD30-CAR TSCM-like cells effectively eradicated Hodgkin lymphoma tumors in vivo, demonstrating a survival advantage and enhanced tumor infiltration compared to more differentiated CAR T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory stem T cells modified with a redesigned CD30-chimeric antigen receptor show an enhanced antitumor effect in Hodgkin lymphoma. Alvarez-Fernández, C., Escribà-Garcia, L., Caballero, AC., et al.[2022]

The study successfully developed a clinical-grade manufacturing process for allogeneic CD19-CAR T cells using donor memory T cells, which expanded significantly (34.2-fold) and showed effective CAR expression (45.5%).

These engineered CD19-CAR T cells demonstrated the ability to recognize and kill CD19-positive cancer cells in laboratory tests and exhibited strong antitumor activity in a model of acute lymphoblastic leukemia (ALL), indicating their potential as a viable treatment option for patients who cannot use autologous CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a cGMP-compliant process to manufacture donor-derived, CD45RA-depleted memory CD19-CAR T cells. Kim-Hoehamer, YI., Riberdy, JM., Zheng, F., et al.[2023]

A new culture protocol successfully activated and proliferated tumor-infiltrating T lymphocytes (TIL) from eight patients with indolent non-Hodgkin's lymphoma, leading to a significant increase in CD8+ T lymphocytes in 6 out of 8 cases.

The expanded CD8+ T lymphocytes demonstrated specific cytotoxicity against autologous malignant B cells, indicating that this method can effectively generate antitumor-specific cytotoxic T cells using a combination of cytokines and irradiated tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation of antitumor-specific cytotoxic T lymphocytes from autologous tumor infiltrating lymphocytes in non-Hodgkin's lymphomas. Chaperot, L., Delfau-Larue, MH., Jacob, MC., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01815749

Study Details | NCT01815749 | Genetically Modified T-cell ... This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating ...

2. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/autologous-cd19car-cd28-cd3zeta-egfrt-expressing-tcm-enriched-t-cells

autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing ... Upon intravenous administration, autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells are directed to CD19-expressing tumor cells, thereby ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11539471/

Advances in CAR-T therapy for central nervous system tumors This review examined the research progress of chimeric antigen receptor T-cell therapy in gliomas, medulloblastomas, and lymphohematopoietic tumors of the ...

4. withpower.com withpower.com/trial/phase-1-burkitt-lymphoma-9-2013-83c16

Genetically Modified T-cells for Non-Hodgkin's Lymphoma In a study, patients with B-cell non-Hodgkin lymphoma who received genetically modified T cells after stem cell transplantation showed promising results, with ...

5. ashpublications.org ashpublications.org/blood/article/127/24/2980/35453/Phase-1-studies-of-central-memory-derived-CD19-CAR

Phase 1 studies of central memory–derived CD19 CAR T–cell ... Key Points. TCM-derived CD19 CAR T–cell therapy is safe for treatment of poor-risk NHL patients undergoing autologous HSCT.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40836026/

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).