Targeted T-Cell and B-Cell Depletion for Hematologic Malignancies

Matched Unrelated Donor and Partially Matched Related Donor Peripheral Stem Cell Transplantation With Alpha/Beta T-Cell and B-Cell Depletion for Patients With Hematologic Malignancies With Targeted ATG Dosing Pilot Study, IDE 13641

This study is testing a new way to prepare patients with blood cancers for stem cell transplants by removing certain immune cells to see if it helps them recover better and stay healthy longer.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 0 Years to 25 Years
• Sex: All
• Sponsor: Medical College of Wisconsin (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT05794880 on ClinicalTrials.gov

What this trial studies

This pilot study focuses on patients with hematologic malignancies who are receiving unrelated or haploidentical related mobilized peripheral stem cells. It utilizes the CliniMACS system for the depletion of alpha/beta T cells and CD19+ B cells, with individualized dosing of ATG based on absolute lymphocyte count (ALC). The study aims to evaluate the impact of this approach on engraftment, graft-versus-host disease (GVHD), and disease-free survival in young patients.

Who should consider this trial

Good fit: Ideal candidates are patients under 25 years old with specific hematologic malignancies in remission.

Not a fit: Patients over 25 years old or those with active disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve engraftment rates and reduce complications in young patients undergoing stem cell transplantation for hematologic cancers.

How similar studies have performed: While similar approaches have been explored, this specific method of targeted T-cell and B-cell depletion with individualized dosing is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Patient age \< 25 years. Both genders and all races eligible.
2. Disease eligibility

   * Acute myeloid leukemia, primary or secondary - Disease status: MRD negative (flow MRD ≤ 0.1%)
   * Myelodysplasia
   * Acute lymphoblastic leukemia - Disease status: MRD negative
   * Chronic myelogenous leukemia - Disease status: chronic phase, accelerated phase or blast crisis now in second chronic phase
   * Mixed lineage or biphenotypic acute leukemia- Disease status: MRD negative
   * Lymphoblastic lymphoma - Disease status: in remission
   * Burkitt's lymphoma/leukemia - Disease status: in remission
   * Lymphoma after relapse - Disease status: in remission
   * Other malignant hematologic diseases in remission (to be approved by PI)
3. Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age (Appendix 1)
4. Evaluation of organ status as per MCW BMT SOP
5. Infectious disease criteria: No active untreated infection. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.
6. Signed consent by parent/guardian or able to give consent if ≥18 years.
7. Negative pregnancy test for patients capable of childbearing potential
8. Sexually active patients capable of child-bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. Sexually active men must agree to use barrier contraceptive for the duration of treatment.

Donor Eligibility:

1. Unrelated donor meets National Marrow Donor Program criteria for donation
2. Infectious disease testing
3. MCW BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
4. Only Peripheral blood stem cells will be used for stem cell source on this study therefore donor must be willing to undergo G-CSF mobilization and stem cell apheresis. Donor matching. High resolution typing at all loci to be performed.
5. Unrelated Donor:

   a. HLA typing of at least 10 alleles is required. Donor must be matched at 9/10 or 10/10 alleles (HLA A, B, C, DRB1, DQB1).Donor and collection center willing to undergo mobilization and apheresis
6. Haploidentical Related Donor:

   1. Haploidentical parent or other related donor: Minimum match level full haploidentical (at least 5/10; HLA A, B, C, DRB1, DQB1 alleles), but use of haploidentical donors with extra matches (e.g. 6, 7, or 8/10) encouraged.

Exclusion Criteria:

1. Patients who do not meet disease, organ, or infectious criteria.
2. No suitable donor
3. Pregnant or lactating patients are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
4. Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy for treatment of disease other than is specified in the protocol. Maintenance or other post-HCT therapy can be considered after discussion with the study PI.
5. Participating in a concomitant Phase 1 or 2 study involving treatment of disease
6. Active malignancy other than eligible disease specified in the protocol. Patients with prior malignancy can be eligible as long as at least 1 year post treatment for that malignancy.

Where this trial is running

Milwaukee, Wisconsin

• Children's Wisconsin — Milwaukee, Wisconsin, United States (RECRUITING)

Study contacts

• Study coordinator: Meredith Beversdorf, RN

Conditions: Leukemia, Acute Myeloid Leukemia in Remission, Myelodysplasia, Acute Lymphoblastic Leukemia in Remission, Chronic Myelogenous Leukemia - Chronic Phase, Chronic Myelogenous Leukemia, Accelerated Phase, Chronic Myelogenous Leukemia With Crisis of Blast Cells, Biphenotypic Acute Leukemia