Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy
Condition: Leukemia; Lymphoma
MeSH terms: Hematologic Neoplasms
Intervention: Total Lymphoid Irradiation; Fludarabine; Cyclophosphamide; Thiotepa; Melphalan; HPC,A Infusion; TC-NK Infusion; G-CSF; Mesna; CliniMACS; Mycophenolate mofetil
Intervention description: Participants receive total lymphoid irradiation over four doses.; Given IV.; Given IV.; Given IV.; Given IV.; Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).; Participants receive infusions of TC-NK.; Participants receive G-CSF subcutaneously or intravenously.
Donors receive G-CSF subcutaneously during cell mobilization.; Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.; The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.; Given intravenously or orally.
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Mechlorethamine; Thiotepa; Fludarabine; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Haploidentical donor transplantation; NK cell

Summary:

      In this study, participants with high-risk hematologic malignancies undergoing hematopoietic
      cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched
      related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a
      haploidentical donor HCT with additional natural killer (NK) cells.

      The investigators anticipate enrollment of 75 donors and 75 recipients.

      PRIMARY OBJECTIVE:

        -  To estimate the rate of successful engraftment at day +42 post-transplant in patients
           who receive haploidentical donor stem cell plus NK cell transplantation with TLI based
           conditioning regimen for high risk hematologic malignancy.

      SECONDARY OBJECTIVES:

        -  Estimate the incidence of malignant relapse, event-free survival, and overall survival
           at one-year post-transplantation.

        -  Estimate incidence and severity of acute and chronic (GVHD).

        -  Estimate the rate of transplant related mortality (TRM) in the first 100 days after
           transplantation.
    

Eligibility criteria:

        Inclusion Criteria - Transplant Recipients:

          -  Age less than or equal to 21 years.

          -  Does not have a suitable MSD or volunteer MUD available in the necessary time for stem
             cell donation.

          -  Has a suitable single haplotype matched (≥ 3 of 6) and family member donor.

          -  High risk hematologic malignancy.

          -  If prior CNS leukemia, it must be treated and in CNS CR

          -  Does not have any other active malignancy other than the one for which this HCT is
             indicated.

          -  No prior allogeneic HCT, and no autologous HCT within the previous 12 months.

          -  Patient must fulfill pre-transplant evaluation

        Inclusion Criteria - Haploidentical Donor:

          -  At least single haplotype matched (≥ 3 of 6) family member

          -  At least 18 years of age.

          -  HIV negative.

          -  Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days
             prior to enrollment (if female).

          -  Not breast feeding.

          -  Regarding eligibility, is identified as either: (1) Completed the process of donor
             eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR (2) Does
             not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical
             need completed by the principal investigator or physician sub-investigator per 21 CFR
             1271.