Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors
Condition: Hematologic Neoplasms; Anemia, Aplastic; Hemoglobinuria, Paroxysmal; Multiple Myeloma
MeSH terms: Multiple Myeloma; Hematologic Neoplasms; Hemoglobinuria; Anemia, Aplastic; Hemoglobinuria, Paroxysmal
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to transplant haploidentical related peripheral blood stem cells
      (PBSCs) that come from a relative such as a parent, sibling, a child or other relative who
      has a half-matched tissue type with the recipient (rather than being completely matched)
      following administration of a reduced-intensity regimen of busulfan, melphalan and
      alemtuzumab.
    

Detailed description: 
      Fewer than 35% of patients who might benefit from allogeneic HCT have an HLA-identical sib.
      Transplantation of peripheral blood stem cells (PBSCs) or bone marrow (BM)from HLA-matched or
      one-locus mismatch unrelated volunteer donors may be an alternative in some patients who lack
      HLA-matched sib donors. Despite increasing numbers of volunteer unrelated donors in national
      and international registries, identification of suitable unrelated donors who are matched
      with the recipient at all HLA-A, -B, -C and -DRB1 loci (8/8 HLA match) or mismatched at one
      of those loci (7/8 HLA match) is still challenging, especially for patients who are
      African-American or multiracial. Additionally, the 3- to 4-month delay between initiation of
      unrelated donor search to HCT is unacceptably long in patients with aggressive hematologic
      malignancies that are likely to relapse or progress during that interval. Transplantation of
      single or dual unrelated umbilical cord blood cells (UCB) units is another alternative,
      although problems with inadequate cell doses, delayed engraftment, graft rejection and
      infection persist in adult recipients of unrelated UCB transplants.

      This is a phase II single-arm open-label study to evaluate the efficacy and safety of
      haploidentical related allogeneic PBSCT using a nonmyeloablative preparative regimen of
      intravenous busulfan (Busulfex®), intravenous melphalan (Alkeran®) and intravenous
      alemtuzumab (Campath®) in subjects who are candidates for related or unrelated allogeneic
      hematopoietic cell transplantation (HCT; transplantation of bone marrow or PBSCs) but who
      lack histocompatible related or unrelated donors. This study will also evaluate immunological
      reconstitution following haploidentical PBSCT by measurement of circulating T cell receptor
      excision circle (TREC)-positive cells, an indicator of thymic output. Systematic analyses of
      TREC-positive cells have not been performed in recipients of haploidentical PBSCT after the
      preparative regimen described in this protocol.
    

Intervention name(s): haploidentical allogeneic PBSC transp
Intervention type(s): Other
Intervention description(s): Days -5 and -4: IV busulfan 3.2 mg/kg/dose daily for 2 days
Day -3: IV melphalan 100 mg/m2 as a single dose
Days -2 and -1: IV alemtuzumab 30 mg/dose daily for 2 days
Day 0: Transplantation of haploidentical related allogeneic peripheral blood stem cells (PBSCs)- target cell dose 10 x 106 donor CD34+ cells per kilogram of recipient weight
Other intervention name(s): Myleran,; Busulfex,; Busulphan; Alkeran,; L-PAM, L-Sarcolysin,; Phenylalanine Mustard; MABCAMPATH®,; CAMPATH®; partially matched family related donor transplant
Intervention MeSH terms: Busulfan; Melphalan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Haploidentical; peripheral blood stem cell transplantation; leukemia; myeloma; Hodgkin's disease; non-Hodgkin's lymphoma