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
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.
- Age between 18 years and 75 years.
- one of these diagnoses: acute myeloid leukemia in remission or relapse, acute
lymphocytic leukemia in remission or relapse, chronic myeloid leukemia, chronic
lymphocytic leukemia, Hodgkin's disease or non-Hodgkin's lymphoma, multiple myeloma,
myelodysplastic syndrome, severe aplastic anemia, or paroxysmal nocturnal
- Subjects with hematologic malignancies must have received at least one previous
course of chemotherapy or biological therapy (i.e., a subject cannot be enrolled on
this study for initial treatment of the malignancy).
- Absence of a healthy related or unrelated volunteer allogeneic donor with whom the
subject is either completely HLA matched at HLA-A, -B, -C and -DRB1 (8/8 HLA match)
or mismatched at no more than one HLA locus (7/8 HLA match).
- Availability of a healthy haploidentical relative (parent, sib or child) who is able
to donate peripheral blood stem cells by apheresis.
- Eligibility for another clinical therapeutic protocol or standard-of-care treatment
that offers higher probability of cure or long-term control of subject's malignancy.
- Availability of a related or unrelated 7/8 or 8/8 HLA-matched allogeneic donor.
- Severe organ dysfunction
- Untreated or progressive central nervous system involvement by malignancy.
- Subject is pregnant or breast feeding.
- Karnofsky score below 50.
- Seropositivity for human immunodeficiency virus (HIV).
- Life expectancy less than 12 weeks with conventional treatments.
- For subjects who are fertile, refusal to practice contraception upon entering this
study and for at least 12 months after PBSCT or after cessation of post-transplant
immunosuppressive treatments, whichever occurs later.