MCW Alpha/Beta T-Cell and B-Cell Depletion With Targeted ATG Dosing
Study Details
Study Description
Brief Summary
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
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Alpha/Beta T cell depletion (TCD) plus CD19+ depletion Alpha beta T cell and B cell depleted allogeneic transplantation with individualized dosing of ATG for patients with hematologic malignancies |
Device: Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi)
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.
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Outcome Measures
Primary Outcome Measures
- 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]
Secondary Outcome Measures
- Evaluate incidence of chronic GVHD [5 years]
- Evaluate time to platelet engraftment [1 years]
- Assess incidence of viral infections [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]
Other Outcome Measures
- 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 [1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient age < 25 years. Both genders and all races eligible.
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Disease eligibility
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Acute myeloid leukemia, primary or secondary - Disease status: MRD negative (flow MRD ≤ 0.1%)
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Myelodysplasia
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Acute lymphoblastic leukemia - Disease status: MRD negative
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Chronic myelogenous leukemia - Disease status: chronic phase, accelerated phase or blast crisis now in second chronic phase
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Mixed lineage or biphenotypic acute leukemia- Disease status: MRD negative
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Lymphoblastic lymphoma - Disease status: in remission
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Burkitt's lymphoma/leukemia - Disease status: in remission
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Lymphoma after relapse - Disease status: in remission
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Other malignant hematologic diseases in remission (to be approved by PI)
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Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age (Appendix 1)
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Evaluation of organ status as per MCW BMT SOP
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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.
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Signed consent by parent/guardian or able to give consent if ≥18 years.
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Negative pregnancy test for patients capable of childbearing potential
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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:
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Unrelated donor meets National Marrow Donor Program criteria for donation
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Infectious disease testing
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MCW BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
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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.
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Unrelated Donor:
- 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
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Haploidentical Related Donor:
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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:
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Patients who do not meet disease, organ, or infectious criteria.
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No suitable donor
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Pregnant or lactating patients are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
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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.
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Participating in a concomitant Phase 1 or 2 study involving treatment of disease
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Medical College of Wisconsin
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IIT-MOSKOP-MABD