Genetically Modified T Cells for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Richter's transformation, NYHA stage III/IV, HIV, others

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

Compensation: Varies

Number of Visits: 12

50 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Using T cells from the patient that have been treated in the laboratory may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated T cells together with cyclophosphamide may kill more cancer cells. PURPOSE: This is a two-stage protocol, consisting of a single-institution phase I safety study and multi-institution phase IIa extension study.

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, since the trial involves chemotherapy, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the treatment Genetically Modified T Cells for Chronic Lymphocytic Leukemia?

Research shows that genetically modified T cells, specifically those with chimeric antigen receptors (CARs), have demonstrated significant anti-tumor effects and long-term disease-free remissions in patients with chronic lymphocytic leukemia (CLL). These studies highlight the potential of CAR T cell therapy to effectively target and kill cancer cells, offering a promising approach for treating CLL. ^{1 2 3 4 5}

Is the treatment with genetically modified T cells for chronic lymphocytic leukemia safe?

Clinical trials have shown that genetically modified T cells, like CAR T cells, can be safe for treating chronic lymphocytic leukemia, but they may cause side effects such as cytokine release syndrome, which is a reaction that can cause fever and low blood pressure. ^{3 4 6 7 8}

How is the treatment Therapeutic Autologous Lymphocytes unique for chronic lymphocytic leukemia?

This treatment uses genetically modified T cells, specifically engineered to target and destroy cancer cells in chronic lymphocytic leukemia. Unlike traditional therapies, it involves modifying the patient's own immune cells to enhance their ability to fight the cancer, offering a more targeted and potentially long-lasting approach. ^{1 2 3 9 10}

Research Team

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients with specific B cell leukemias or lymphomas that have either returned after treatment or didn't respond to chemotherapy. They must be confirmed at MSKCC, expected to live more than 3 months, and meet certain health criteria like kidney function and blood counts.

Inclusion Criteria

I have a type of low-grade B-cell blood cancer.

Must have a life expectancy of > 3 months

My heart is strong enough for treatment (LVEF ≥40%).

Exclusion Criteria

I have severe heart issues, including recent heart failure or heart attack.

I have HIV, hepatitis B, or hepatitis C.

My CLL has transformed into a more aggressive form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy

Varies based on dose escalation steps

Multiple visits for dose escalation and monitoring

Phase IIa Extension

Co-infusion of 19-28z and CART-19:CD3z-4-1BB+ modified T cells at the MTD determined from phase I

Duration not specified

12 patients enrolled for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Cyclophosphamide
• Therapeutic Autologous Lymphocytes

Trial Overview The study tests if T cells from the patient, modified in a lab to target cancer cells, combined with cyclophosphamide chemotherapy can effectively kill cancer cells. It's conducted in two stages: an initial safety study followed by a larger efficacy study.

Participant Groups

Group I: Patients with CLL or indolent B-cell lymphoma Experimental Treatment 2 Interventions

The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy.Step 1, a cohort of pts will receive the lowest planned dose of 19-28z+ modified T cells. Step 2, a cohort of pts will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. If less than 33% of pts in the cohort experience unanticipated dose-limiting toxicity,Step 3, a cohort of pts will be treated with the investigator's choice conditioning chemotherapy followed by the higher dose of 19-28z+ modified T cells. If less than 33% of pts in the initial cohort (Step 3) experience unanticipated dose-limiting toxicity, the cohort in Step 3 may be expanded to include up to 15 pts. In Step 3, an additional cohort of Waldenstrom's Macroglobulinemia (WM) pts will be treated with the investigator's choice conditioning chemotherapy followed by 19-28z+ T cells.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Recent advancements in T-lymphocyte based therapies, particularly through donor lymphocyte infusion and ex vivo expansion of antigen-specific cytotoxic T lymphocytes, have shown promising sustained antitumor effects in patients with virus-associated lymphomas, such as those related to Epstein-Barr virus.

The development of robust gene transfer methodologies to human T lymphocytes is rapidly evolving, providing new opportunities for enhancing the efficacy and specificity of T-cell based therapies in treating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. Hoyos, V., Savoldo, B., Dotti, G.[2021]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving remission rates as high as 90% in relapsed/refractory acute lymphoblastic leukemia (ALL), but lower response rates in chronic lymphocytic leukemia (CLL) highlight the need for ongoing research to improve outcomes.

Long-term follow-up indicates that CAR T cell therapy may provide durable remissions, but the emergence of escape pathways necessitates combinatorial treatment strategies and careful toxicity management to enhance safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia. Singh, N., Frey, NV., Grupp, SA., et al.[2018]

References

1. China pubmed.ncbi.nlm.nih.gov

[Anti-cD20scFv/CD80/CD28/zeta specific T lymphocytes eradicate primary chronic lymphocytic leukemia cells in vitro]. [2018]

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

Chasing cancer with chimeric antigen receptor therapy. [2021]

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

CARs in chronic lymphocytic leukemia -- ready to drive. [2021]

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

Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Stem Cell-Derived Immune Cells for Off-the-Shelf Cancer Immunotherapies. [2022]

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

Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds. [2018]

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

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Genome editing of therapeutic T cells. [2022]

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

CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia. [2018]