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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating chronic lymphocytic leukemia (CLL) and similar blood cancers by using patients' own T cells, modified in a lab to better fight cancer. The trial evaluates the safety of these modified T cells, both alone and in combination with the chemotherapy drug cyclophosphamide. It targets individuals whose cancer has returned or hasn't responded to previous treatments. Suitable candidates include those with certain blood cancers, like CLL or follicular lymphoma, who still have residual cancer after other therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative 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, 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.

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

Studies have shown that 19-28z CAR T cells, specially altered immune cells, have been used to treat certain blood cancers, such as chronic lymphocytic leukemia (CLL) and other B-cell conditions. Research indicates these T cells specifically target cancer cells.

In earlier studies, patients who received these CAR T cells experienced some side effects, but the treatment was generally well-tolerated. Common side effects included fever and low blood pressure, which were usually manageable. Out of 20 patients treated with these T cells, the treatment demonstrated promising safety and tolerability.

Additionally, when combined with chemotherapy drugs like cyclophosphamide, the CAR T cells attacked cancer cells more effectively. Patients undergoing this combination treatment did not report unexpected severe side effects in more than a third of cases.

Overall, research suggests that 19-28z CAR T cells are relatively safe for treating CLL, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about genetically modified T cells for treating Chronic Lymphocytic Leukemia (CLL) because they take a novel approach by harnessing the body's own immune system. Unlike standard treatments like chemotherapy and monoclonal antibodies, which broadly target cancer cells, this method involves engineering the patient's T cells to specifically recognize and attack cancer cells. This is achieved through a new mechanism called CAR T-cell therapy, which equips T cells with a special receptor (19-28z CAR) that enhances their ability to find and destroy cancer cells. This targeted approach has the potential to offer more precise and effective treatment with fewer side effects compared to traditional methods.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that CAR-T cell therapy, which involves modifying a person's own T cells to better fight cancer, holds potential for treating certain cancers. In Chronic Lymphocytic Leukemia (CLL), results have been mixed. CAR-T cells have not been as effective in CLL as in other B-cell cancers, but some studies have found significant tumor reduction in patients with difficult-to-treat cases. In this trial, participants will receive 19-28z CAR T cells, which have demonstrated strong benefits in some studies. Some participants will receive these modified T cells alone, while others will receive them in combination with chemotherapy drugs like cyclophosphamide, which may enhance the effectiveness of killing cancer cells. ^{1 2 4 6 7}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

Must have a life expectancy of > 3 months

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11178044/

CAR-T Cells in Chronic Lymphocytic Leukemia - PMC Although CAR-T cells were initially used for the treatment of CLL, their efficacy in CLL patients was lower than in other B-cell malignancies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4684949/

Efficacy and Toxicity Management of 19-28z CAR T Cell ... We next demonstrated potent antitumor benefit after infusing CD19-targeted 19-28z CAR T cells into five adults with relapsed or refractory B cell acute ...

3. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05963217

NCT05963217 | Study of TBI-2001(Autologous CD19 ... This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721012975

Driving Out Chronic Lymphocytic Leukemia With CAR T Cells In this comprehensive review we explore novel targets for CAR T cell therapy in CLL and highlight the promising results of CAR T cell trials reported to date.

6. ashpublications.org ashpublications.org/blood/article/118/18/4817/29377/Safety-and-persistence-of-adoptively-transferred

Safety and persistence of adoptively transferred autologous ... We demonstrate rapid trafficking of 19-28z+ T cells to sites of tumor involvement and report on the short-term persistence and function of the adoptively ...

7. insight.jci.org insight.jci.org/articles/view/122627

Safety and tolerability of conditioning chemotherapy ... Herein, we report safety data and long-term follow-up of 20 patients with R/R CLL and indolent B-NHL treated with 19–28z CAR T cells, including the 8 patients ...