CD19-CAR T Cells for Acute Lymphoblastic Leukemia

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: HLA-identical sibling, Other malignancy, Prior HCT, Pregnant, Infections, 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 explores a new treatment for children with high-risk CD19 positive B-cell ALL. It focuses on using special immune cells called CD19-CAR T cells (a type of immunotherapy) after a blood cell transplant from a partially matched family member. The goal is to determine the safety and effectiveness of this combination. Children with difficult-to-treat leukemia who rely on transplants are suitable candidates for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

What prior data suggests that this method is safe for pediatric patients with high-risk CD19 positive leukemia?

Research has shown that CD19-CAR T cells offer promising safety results for treating certain blood cancers. In past studies, these specially modified cells, designed to attack cancer cells, were well-tolerated by most patients. Some common side effects, such as fever and tiredness, were reported but generally remained manageable.

Similarly, previous research has demonstrated the safety of TCRαβ+ T cell-depleted haploidentical hematopoietic cell transplantation. This method uses donor cells that partially match the patient and has been successful in children with blood cancers. The procedure has shown low rates of serious side effects, such as graft-versus-host disease (GVHD), where donor cells attack the patient's body.

Both treatments remain in the early stages of research for this specific use. While initial findings are encouraging, more data is needed to fully understand their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for acute lymphoblastic leukemia, which often involve chemotherapy and radiation, this investigational approach uses a two-part strategy combining TCRαβ+ T cell-depleted haploidentical hematopoietic cell transplantation and CD19-CAR T-cell therapy. The innovation here lies in the use of CD19-CAR T cells, which are engineered to specifically target and destroy leukemia cells by recognizing the CD19 protein present on their surface. Additionally, the TCRαβ+ T cell depletion technique helps reduce the risk of graft-versus-host disease, making transplantation safer. Researchers are excited about this treatment because it promises a more precise attack on cancer cells while minimizing some of the severe side effects associated with conventional therapies.

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

Research has shown that a treatment called CD19-CAR T cells may help treat certain types of leukemia, such as acute lymphoblastic leukemia (ALL). These specially engineered cells can find and destroy cancerous B-cells with the CD19 protein. In this trial, participants will receive a combination of treatments. One arm involves a type of transplant that removes certain T cells from a donor's blood, which has been linked to lower rates of graft-versus-host disease (GVHD), a complication where the donor's cells attack the patient's body. This transplant method can lead to better survival rates and longer periods without the disease. Combining these treatments might improve outcomes for patients whose CD19+ B-cell cancers have returned or are not responding to other treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Swati Naik, MBBS

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children with high-risk CD19 positive leukemia (ALL) or lymphoma who have relapsed or are refractory, and can receive blood cells from a partially matched family donor. Specific eligibility details aren't provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

Donor must have completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance OR have a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271

I am 21 years old or younger.

My previous brain leukemia has been treated and is now in remission.

Exclusion Criteria

Recipient is pregnant (if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment)

Recipient is breastfeeding

Donor is pregnant (negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment if female)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive a conditioning regimen comprising ATG, Fludarabine, Cyclophosphamide, Melphalan, and Thiotepa before transplantation

1-2 weeks

Transplantation and Initial Monitoring

Infusion of TCRαβ depleted progenitor cells on day 0, followed by CD19-CAR(Mem) T cell product as early as day +14. Patients are monitored for safety and efficacy of the infused CAR T-cell product

4 weeks

Follow-up

Participants are monitored for safety and effectiveness, including assessment of toxicities and survival outcomes

100 days

Long-term Follow-up

Participants are monitored for relapse-free survival, GVHD, and other long-term outcomes

3 years

What Are the Treatments Tested in This Trial?

Interventions

• CD45RA-depleted CD19-CAR T Cell
• TCRαβ+ T Cell-depleted Haploidentical Hematopoietic Cell Transplantation

Trial Overview The study tests a new method of transplanting blood cells after using CD45RA-depleted CD19-CAR T Cells following TCRαβ+ depleted haploidentical hematopoietic cell transplantation. It aims to assess safety, feasibility, survival rates, graft-versus-host disease occurrence, and immune-related side effects.

How Is the Trial Designed?

Group I: HAPALL Treatment Experimental Treatment 8 Interventions

Patients receive a conditioning regimen that will comprise of ATG, Fludarabine, Cyclophosphamide. Melphalan and Thiotepa. Following the conditioning regimen, patients receive infusion of TCRαβ depleted progenitor cell infusion on day 0. Then as early as day + 14 patients will receive the previously manufactured CD19-CAR(Mem) T cell product. Patients will then be monitored for safety and efficacy of the infused CAR T-cell product, Cells for infusion are prepared using the CliniMACS system.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07257419?cond=cancer

CD45RA-depleted CD19-CAR T Cell Consolidation After ... The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10286828/

Development of a cGMP-compliant process to manufacture ... Here we optimized conditions for clinical-grade manufacturing of allogeneic CD19-CAR T cells using CD45RA-depleted donor memory T cells for a planned clinical ...

3. ashpublications.org ashpublications.org/bloodadvances/article/6/19/5582/485027/Haploidentical-donor-derived-memory-CAR-T-cells

Haploidentical donor-derived memory CAR T cells Depletion of naïve (CD45RA+) T cells reduces the frequency of alloreactive T cells and is used to process hematopoietic stem cell grafts and ...

4. trial.medpath.com trial.medpath.com/clinical-trial/9aea73761e0b0a3a/nct07257419-cd45ra-depleted-cd19-car-t-cell-haploidentical-transplant-cd19-all

CD45RA-depleted CD19-CAR T Cell Consolidation After TCR ... The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1201971224001140

TCRαβ-depleted hematopoietic stem cell transplant and ... A 6-year-old girl with relapsed B cell acute lymphoblastic leukemia achieved second complete remission after autologous CAR T-cell therapy. Unfortunately ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07257419?lastUpdPost=2020-03-16_

CD45RA-depleted CD19-CAR T Cell Consolidation After ... Primary Objective: - To assess the safety and feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+ depleted haploidentical donor ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123023248

TCRαβ/CD19 cell–depleted HLA-haploidentical ... We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of TCRαβ/CD19-depleted ...