Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
Condition: Hematologic Malignancy
MeSH terms: Neoplasms; Hematologic Neoplasms; Graft vs Host Disease
Intervention: ClinicMACs
Intervention description: The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Graft vs. Host Disease; Hematologic Malignancy

Summary:

      This research study is studying the removal of a subset of white blood cells (called
      alpha/beta T cells) from the donor product using a cell separation device before the product
      is transplanted into the participant.

      The device used to remove the α/βT cells in this study is:

      -CliniMACS® TCR α/β Reagent System
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnoses and stage at time of transplant admission:

               -  Acute leukemia (AML or ALL or MPAL) in first or subsequent remission

               -  Myelodysplastic syndromes (MDS) with <10% marrow blasts

               -  Myeloproliferative neoplasm (MPN) with <10% marrow blasts

               -  CMML with less than 10% marrow blast

               -  CML accelerated phase or second or subsequent chronic phase

               -  Non-Hodgkin's lymphoma in PR or CR2 or beyond

               -  Hodgkin lymphoma in PR or CR2 or beyond

          -  Age 18-65 years

          -  Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C,
             DRB1 and DQB1, based on allele level typing.

          -  Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)

          -  Patient deemed to be appropriate candidate for myeloablative conditioning
             transplantation.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patient with active HIV infection

          -  Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)

          -  Prior allogeneic hematopoietic stem cell transplantation

          -  Impaired cardiac function- ejection fraction < 40%

          -  Impaired pulmonary function- pretransplant FEV1, DLCO < 50%

          -  Impaired renal function, based on

             --Serum creatinine > 2.0 mg/dl

          -  Impaired liver function unrelated to primary disease, based on

             --ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or
             suspected Gilbert's disease)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Women who are pregnant or breast feeding. Women of child bearing potential must have a
             negative serum pregnancy test at study entry.

          -  Participants who are receiving any other investigational agents are eligible but such
             agent must be discontinued before admission for HSCT, and if resumption of
             investigation agent is planned after HSCT, this must be approved by the study PI.

          -  Participants with known active CNS disease. CNS disease that has been treated is
             eligible