Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy
Condition: MDS; Leukemias; Lymphomas
MeSH terms: Lymphoma; Leukemia
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to see if giving high dose chemotherapy and total body
      irradiation before and repeating high dose chemotherapy after a bone marrow transplant could
      reduce the incidence of graft rejection and disease for patients with blood cancers
    

Detailed description: 
      Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or
      nonmyeloablative conditioning, is a potentially curative treatment for a variety of
      hematologic malignancies and non-malignant hematologic disorders. Of all the potential
      sources of allografts, transplantation of stem cells from a human leukocyte antigen
      (HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and
      progression-free survival. Unfortunately, only about a third of candidates for alloBMT have
      HLA-matched siblings.

      For patients who lack HLA-matched siblings, there are three alternative sources of stem cells
      for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially
      HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA
      haplotype with each biological parent or child and half of siblings, an eligible
      haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical
      BMT has been associated with significant risks of graft rejection and severe GVHD, which are
      manifestations of excessive alloreactivity by host and donor T cells, respectively.

      The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that
      have been rigorously depleted of mature T cells or selectively depleted of alloreactive T
      cells, but the risks of serious infection and death from prolonged immune compromise in these
      patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive antineoplastic
      agent that has an established role in conditioning for alloBMT.

      Typically, the drug is administered prior to transplantation to prevent graft rejection by
      suppressing the host immune system. However, pre-transplantation conditioning with Cy
      increases the risk of GVHD following allogeneic T cell infusion in mouse models. In contrast,
      administration of a properly timed, high dose of Cy after BMT inhibits both graft rejection
      and GVHD.
    

Intervention name(s): Busulfan; Cyclophosphamide; Total body irradiation
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): Participant will receive Busulfan injections, 4 times a day for 4 days with dilantin prophylaxis (in patients 10 years of age or older). Busulfan levels in the blood will be measured and dose adjusted, if needed.; Patient will receive Cy by IV once a day for 2 days.; Patients will receive TBI once a day for 4 days.
Other intervention name(s): Cy; Cytoxan; CTX; TBI
Intervention MeSH terms: Cyclophosphamide; Busulfan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Lymphoma; Hematologic malignancies; ALL; AML; MDS; Transplantation; Mismatched; Haploidentical; Busulfan; Cyclophosphamide; Cellcept; Tacrolimus; TBI; CMMOL; CML; JMML