Cell-Depleted Donor Grafts for Blood Cancers

Overseen By Melinda Triplet, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nationwide Children's Hospital

Disqualifiers: No suitable donor, Anti-HLA antibodies, Murine protein allergy, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for blood cancers using a special donor cell transplant called Partially Matched Related Donor Hematopoietic Cell Transplantation. The researchers aim to evaluate the treatment's effectiveness and its impact on the risk of GVHD, a condition where donor cells attack the patient's body. Participants may qualify if they have blood cancer, lack a matching sibling donor, and require a second transplant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that the CliniMACS TCRαβ/CD19 depletion system can make stem cell transplants safer. This system removes certain cells from the donor's stem cells to reduce the risk of graft-versus-host disease (GVHD), which occurs when the donor's cells attack the patient's body. Studies have found this method reliable and free of major issues.

Patients who received these specially prepared stem cells experienced fewer problems with GVHD, indicating that the treatment is safe and well-tolerated. The process of removing specific cells, such as TCRαβ and CD19 cells, has effectively prevented serious side effects. Overall, current evidence suggests this treatment method is promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the cell-depleted donor grafts for blood cancers because they offer a new approach to transplantation. Unlike traditional hematopoietic cell transplants, which can result in serious immune reactions due to mismatched cells, this method uses CliniMACS Isolation to remove specific immune cells (αβTCR+ and CD19+ cells) from the donor graft. This targeted depletion reduces the risk of graft-versus-host disease while still allowing the body to fight cancer effectively. By potentially increasing compatibility and safety, this innovative approach could make transplants more accessible and successful for patients with limited donor options.

What evidence suggests that the CliniMACS® TCRαβ/CD19 Combined Depletion System is effective for blood cancers?

Research has shown that using a special type of cell-depleted graft, like the one studied in this trial, can lower the risk of graft-versus-host disease (GVHD), a common issue after stem cell transplants. In this trial, the CliniMACS Isolation arm processes the mobilized peripheral blood cell collection to deplete αβTCR+ cells and CD19+ cells from the graft. One study found that removing certain donor cells from the graft before administration reduces GVHD while still allowing the transplant to fight blood cancers effectively. Another analysis found this method especially promising for patients receiving transplants from partially matched donors. Early findings suggest this approach can safely improve outcomes by preventing harmful immune responses without losing the transplant's benefits. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 30 years old with certain blood cancers or preleukemia conditions. They must have suitable organ function, may be eligible for a second transplant if needed, and cannot have active untreated infections. Participants need effective contraception if of childbearing potential and lack an HLA matched sibling donor.

Inclusion Criteria

I am using or willing to use effective birth control if I can have children.

I do not have a sibling donor that matches my HLA type.

My organ functions meet specific health standards.

Exclusion Criteria

I have specific antibodies against donor tissues.

Patient reports a history of allergic reactions to murine protein

I do not have a suitable donor available for my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo haploidentical hematopoietic cell transplantation using an αβTCR/CD19+ cell depleted graft

4-6 weeks

Multiple visits for transplantation and monitoring

Follow-up

Participants are monitored for safety, immune reconstitution, and incidence of GVHD

4 years

Regular follow-up visits over 4 years

What Are the Treatments Tested in This Trial?

Interventions

• CliniMACS® TCRαβ/CD19 Combined Depletion System
• Partially Matched Related Donor Hematopoietic Cell Transplantation
• αβTCR/CD19+ Cell Depleted Graft

Trial Overview The study tests the CliniMACS® TCRαβ/CD19 Depletion System in partially matched related donor hematopoietic cell transplantation. It aims to observe how quickly patients recover their blood cells and the occurrence of graft-versus-host disease after the procedure.

How Is the Trial Designed?

Group I: CliniMACS Isolation Experimental Treatment 1 Intervention

The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft.

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05968170

TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant The CliniMACS CD34+ Reagent System decreases the risk of developing GVHD by efficiently removing donor T-cells from the graft prior to infusion by enriching ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04249830

NCT04249830 | Stem Cell Transplant From Donors After ... The purpose of the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 is to improve the safety and efficacy of allogeneic HLA-partially matched related or ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0966327425000486

Comprehensive up-to-date analysis on TCRαβ/CD19 ... This meta-analysis assesses the efficacy of TCRαβ+/CD19+ depleted hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematological ...

4. ashpublications.org ashpublications.org/blood/article/143/3/279/498045/TCR-CD19-cell-depleted-HLA-haploidentical

TCRαβ/CD19 cell–depleted HLA-haploidentical ... T-cell receptor (TCR)αβ/CD19 cell depletion has emerged as an effective graft manipulation strategy for preventing graft-versus-host disease ( ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6944939/

Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy We report the results of the first ten TCRαβ+ and B cell depletion procedures for clinical use performed at our centre.