MCW Alpha/Beta T-Cell and B-Cell Depletion With Targeted ATG Dosing

Official title

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

Overview

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

Interventions

• 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.

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 [Time frame: 1 year]

Secondary outcome measures (6)

• Evaluate incidence of chronic GVHD [Time frame: 5 years]
• Evaluate time to platelet engraftment [Time frame: 1 years]
• Assess incidence of viral infections [Time frame: 2 years]
• Evaluate incidence of relapse/progressive disease [Time frame: 2 years]
• Evaluate incidence of treatment-related mortality (TRM). [Time frame: 2 years]
• Evaluate overall and relapse free survival (RFS) at 1 year [Time frame: 1 years]

Eligibility criteria

Inclusion criteria

• Patient age < 25 years. Both genders and all races eligible.
• 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)
• 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:

• 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

• Patients who do not meet disease, organ, or infectious criteria.
• No suitable donor
• Pregnant or lactating patients are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
• 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.
• Participating in a concomitant Phase 1 or 2 study involving treatment of disease
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Children's Wisconsin — Milwaukee

Identifiers

NCT: NCT05794880 · IIT-MOSKOP-MABD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗