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This is a single arm pilot study for patients with hematologic malignancies receiving unrelated or haploidentical related mobilized peripheral stem cells (PSCs) using the CliniMACS system for alpha/beta T cell depletion plus CD19+ B cell depletion with individualized ALC-based dosing of ATG to study impact on engraftment, GVHD, and disease free survival
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alpha/Beta T cell depletion (TCD) plus CD19+ depletion | Experimental | Alpha beta T cell and B cell depleted allogeneic transplantation with individualized dosing of ATG for patients with hematologic malignancies |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi) | Device | Participants in this study will receive a blood stem cell transplant, which will use an investigational device called the CliniMACs device to remove alpha/beta T cells and B cells from the blood cells collected from the donor. This is called T cell depletion and B cell depletion. |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate incidence and extent of aGVHD and engraftment in patients receiving alpha/beta T cell depleted and CD19+ B cell depleted stem cell transplant with individualized ALC-based dosing of ATG | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate incidence of chronic GVHD | 5 years | |
| Evaluate time to platelet engraftment | 1 years | |
| Assess incidence of viral infections |
| Measure | Description | Time Frame |
|---|---|---|
| Assess tempo of CD4+ T cell reconstitution. | 2 years | |
| Assess tempo of immune reconstitution. | 2 years | |
| Assess ATG exposure using pre- and post- HCT AUC estimates using ATG dosing module |
Inclusion Criteria:
Patient age < 25 years. Both genders and all races eligible.
Disease eligibility
Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age (Appendix 1)
Evaluation of organ status as per MCW BMT SOP
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.
Signed consent by parent/guardian or able to give consent if ≥18 years.
Negative pregnancy test for patients capable of childbearing potential
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:
Unrelated donor meets National Marrow Donor Program criteria for donation
Infectious disease testing
MCW BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
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.
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
Haploidentical Related Donor:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Meredith Beversdorf, RN | Contact | 414-266-5891 | mbeversdorf@childrenswi.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
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|
| 2 years |
| Evaluate incidence of relapse/progressive disease | 2 years |
| Evaluate incidence of treatment-related mortality (TRM). | 2 years |
| Evaluate overall and relapse free survival (RFS) at 1 year | 1 years |
| 1 year |
| ID | Term |
|---|---|
| D007938 | Leukemia |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D015456 | Leukemia, Biphenotypic, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D002051 | Burkitt Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D009196 | Myeloproliferative Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
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