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

51 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 on other investigational drugs, certain doses of corticosteroids, or if you have an active autoimmune disease requiring systemic treatment.

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

Research shows that similar treatments using modified T cells, like CD19 CAR T cells, have been effective in treating B-cell malignancies, including Non-Hodgkin's Lymphoma. In one study, 75% of patients treated with a similar T cell therapy were progression-free at one year, indicating promising results for this type of treatment. ^{1 2 3 4 5}

Is the Memory-Enriched T Cell treatment safe for humans?

The Memory-Enriched T Cell treatment has been tested in clinical trials for non-Hodgkin's lymphoma, showing it to be generally safe with manageable side effects. Common side effects include mild cytokine release syndrome (a reaction where the immune system releases too many proteins into the blood too quickly) and no severe neurotoxicity (damage to the nervous system). ^{3 4 6 7 8}

How is the treatment for Non-Hodgkin's Lymphoma using memory-enriched T cells different from other treatments?

This treatment uses specially engineered T cells that are enriched for memory characteristics, which may help them persist longer and be more effective in fighting cancer. Unlike standard treatments, these T cells are designed to target specific cancer markers, potentially leading to better outcomes for patients with relapsed or refractory Non-Hodgkin's Lymphoma. ^{4 5 6 9 10}

What is the purpose of this trial?

This phase I trial studies the highest possible dose of memory enriched T cells that can be given following standard stem cell transplant before unmanageable side effects are seen in patients with B-cell non-Hodgkin lymphoma that has returned after previous treatment. A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Memory enriched T cells will be made from a patient's own T cells that are genetically modified in a laboratory. This means that the T cells are changed by inserting additional pieces of deoxyribonucleic acid (genetic material) into the cell to make it recognize and kill lymphoma cells. Memory enriched T cells may kill the cells that are not killed by stem cell transplant and may lower the chances of the cancer recurring.

Research Team

Elizabeth Budde, MD, PhD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Differentiation of antitumor-specific cytotoxic T lymphocytes from autologous tumor infiltrating lymphocytes in non-Hodgkin's lymphomas. [2019]

2. Australia 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. [2022]

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

Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. [2022]

4. United States 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. [2023]

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

CD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN-γ Production Profile. [2021]

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

Development of a cGMP-compliant process to manufacture donor-derived, CD45RA-depleted memory CD19-CAR T cells. [2023]

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

CAR T cell manufacturing from naive/stem memory T lymphocytes enhances antitumor responses while curtailing cytokine release syndrome. [2022]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale. [2021]

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

Comparison of naïve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer. [2021]