Modified T-Cell Therapy for Acute Lymphoblastic Leukemia

Not currently recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Glucocorticosteroids

Disqualifiers: Active malignancies, HIV, Hepatitis, Pregnancy, 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 aims to test the safety of a new treatment for individuals with acute lymphoblastic leukemia (ALL) that has returned to their bone marrow. The treatment uses modified T cells, derived from the patient's own blood, to combat the leukemia. The trial includes two groups: one for patients with visible disease in their bone marrow and another for those without visible disease. This trial may suit patients under 26 whose leukemia has returned or not responded to treatment, particularly if they have CD19+ B-ALL involving the bone marrow. 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 new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic chemotherapy, you need to stop it at least 2 weeks before the infusion or apheresis, except for certain medications like hydroxyurea or oral maintenance chemotherapy, which can continue if the dose hasn't increased for 2 weeks. Always discuss with your doctor before making any changes to your medication.

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

Research has shown that CAR T-cell therapy, which uses modified T cells, can be effective but also raises safety concerns. In one study, 18 out of 20 patients achieved complete remission with this treatment. However, it can cause serious side effects, including high relapse rates, cytokine release syndrome (a severe immune reaction), and neurological problems. Safety remains a major focus, especially in early studies like this one. Considering these risks is important when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about modified T-cell therapy for acute lymphoblastic leukemia (ALL) because it uses a cutting-edge approach called CAR T-cell therapy. Unlike traditional treatments, such as chemotherapy and radiation, which attack both healthy and cancerous cells, this therapy involves reprogramming a patient's own T cells to specifically target and kill leukemia cells. The modified T cells are designed to recognize and bind to cancer cells more effectively, potentially leading to more precise and less harmful treatment. This targeted approach not only aims for better outcomes but also hopes to reduce the severe side effects often associated with conventional treatments.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that a type of modified T-cell therapy, called CAR T-cell therapy, holds promise for treating acute lymphoblastic leukemia. In earlier studies, about 88% of patients experienced a complete response, meaning their cancer was not detectable after treatment. This suggests the therapy can be very effective for many people. In this trial, participants will receive modified T-cells designed to target cancer cells precisely, reducing the risk of harming healthy cells. This precision makes the treatment not only effective but also potentially safer. ^{1 2 6 7 8}

Who Is on the Research Team?

Kevin Curran

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for pediatric and young adult patients with a relapse of B-cell acute lymphoblastic leukemia. Eligible participants include those diagnosed at age ≥13 years, with specific genetic markers or high-risk features, and who are in their first or subsequent bone marrow relapse.

Inclusion Criteria

My leukemia was CNS-3 at diagnosis.

There is still evidence of cancer cells in your bone marrow after the initial treatment.

My leukemia is either t(17;19) ALL or Ph-Like ALL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy prior to T cell infusion

1-2 weeks

T Cell Infusion

Participants receive 19-28z+ T cells infusion over 1 to 2 days

1-2 days

Follow-up

Participants are monitored for safety and effectiveness after T cell infusion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Modified T cells

Trial Overview The study tests the safety of modified T-cells made from the patient's own blood to treat leukemia that has returned. It aims to determine a safe dose for these special cells after standard chemotherapy regimens.

How Is the Trial Designed?

Group I: Cohort 2 (Morphologic Disease) Experimental Treatment 3 Interventions

Pts with morphologic evidence of disease at the time of T cell infusion, (≥5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Pts with increased blasts (5-10% blasts) that are immunophenotypically consistent with recovering marrow from prior re-induction chemo may be treated under Cohort 1 with approval of the participating site PI. Cohort 2 pts will get conditioning chemo followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of EOP T cells, under or over estimation of CAR modified T-cells may occur. Pts may get up to 35% over total cell dose with approval by the participating site PI. Both cohorts, pts will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion \& did not experience any non-hematologic grade 4 toxicities.

Group II: Cohort 1 (MRD) Experimental Treatment 3 Interventions

Patients with no morphologic evidence of disease at the time of T cell infusion, (\<5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Cohort 1 patients will receive conditioning chemotherapy followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of End of Production (EOP) T cells, under or over estimation of CAR modified T-cells may occur. Patients may receive an altered fractionation of the total doses (e.g. ½ on Day 0 and ½ on Day +1) or up to 35% over total cell dose with approval by the participating site PI. In both cohorts, patients will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion and did not experience any non-hematologic grade 4 toxicities.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Dana-Farber Cancer Institute:Dana- Farber/Children's Hospital

Collaborator

Trials

1

Recruited

20+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11095278/

Comprehensive analysis of the efficacy and safety of CAR ... The principal advantage of CAR T-cell therapy is the high specificity, leading to reduced occurrence of side effects which are beneficial for ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/11/2763/536292/Real-world-outcomes-for-young-adult-patients

Real-world outcomes for young adult patients receiving CD19 ... Key PointsReal-world efficacy among YAs receiving CD19 CAR T was comparable irrespective of CAR T construct.CRS and ICANS were observed more ...

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

Efficacy and Toxicity Management of 19-28z CAR T Cell ... The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell ...

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

CAR-T cell therapy for cancer: current challenges and ... 2-targeted CAR has proven effective in treating gastrointestinal tumors in a study including 37 patients (NCT04196413), with an overall response ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124025461

The present and future of CAR T-cell therapy for adult B- ... Long-term remission rates are inversely correlated with age (30%-40% in adults; >90% in children), and relapsed/refractory (R/R) disease in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6745916/

Chimeric Antigen Receptor T-Cell Therapy Clinical Results ... They estimated a 12-month EFS of 50.8% (95% CI 36.9 to 69.9%) and OS of 69.5% (95% CI 55.8 to 86.5%) with a median follow-up of 9.6 months. CAR-modified T-cells ...

7. ashpublications.org ashpublications.org/blood/article/145/14/1485/517958/The-present-and-future-of-CAR-T-cell-therapy-for

The present and future of CAR T-cell therapy for adult B-cell ALL Prior ALL treatments may compromise T-cell fitness, but for most CAR-T products, there are no absolute numeric lymphocyte cutoffs for leukapheresis. Early ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000096

CAR T-cells for T-cell acute lymphoblastic leukemia The results of the phase I study described a complete remission for 18 out of 20 infused patients. After a median follow up of 6.3 months 15 patients remained ...