Study of Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Hematopoietic Malignancies Including Those That Are Challenging to Engraft
Condition: Hematopoietic Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Cyclophosphamide
Intervention description: Shortened duration immunosuppression following nonmyeloablative peripheral blood stem cell transplant with high dose post transplantation cyclophosphamide in malignancies to engraft.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Hematopoietic Malignancies; Nonmyeloablative Peripheral Blood Stem Cell Transplant; Posttransplantation

Summary:

      This is an open label phase II single arm study of peripheral blood stem cell transplantation
      and posttransplantation cyclophosphamide, using HLA full match or haploidentical related
      donors, in hematological malignancies including those difficult to engraft. The objective of
      this study is to evaluate the safety and feasibility in nonmyeloablative, partially
      HLA-mismatched or HLA-matched PBSC transplant from haploidentical donors or fully matched
      donors with post-grafting immunosuppression that includes high-dose cyclophosphamide,
      tacrolimus, and Mycophenolate mofetil (MMF).
    

Eligibility criteria:

        Inclusion Criteria:

        The following are eligibility for study entry and transplantation.

          -  Presence of a suitable related, HLA-haploidentical or HLA-matched stem cell donor

          -  The donor and recipient must be identical at least one allele of each of the following
             genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is
             therefore required for related donors, and will be considered sufficient evidence that
             the donor and recipient share one HLA haplotype.

          -  Eligible diagnoses:

          -  Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia [CMML] with
             at least one poor risk factor

          -  No active extramedullary leukemia or known active CNS involvement by malignancy. Such
             disease treated into remission is permitted.

          -  Any previous autologous HSCT must have occurred at least 3 months prior to start of
             conditioning

          -  No previous allogeneic HSCT

          -  Adequate end-organ function Note: Infection is permitted if there is evidence of
             response to medication. Eligibility of HIV infected patients will be determined on a
             case-by-case basis.

          -  ECOG performance status < 2 or Karnofsky or Lansky score > 60.

          -  Age > 18 years and older.

          -  Not pregnant or breast-feeding.

          -  No uncontrolled infection.

        Eligible diagnoses:

          -  Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia [CMML] with
             at least one of the following poor-risk features

          -  SLL or CLL with 17p deletion, or with progression < 6 months after second or greater
             treatment regimen. Must have the following to be an acceptable candidate as well:

               -  < 20% of bone marrow cellularity involved by SLL/CLL (to lower risk of graft
                  rejection)

               -  No lymph nodes > 5 cm in any dimension

               -  No massive splenomegaly, defined as > 6 cm below the left costal margin

          -  T-cell PLL in PR or better prior to transplantation. Must also have < 20% of bone
             marrow cellularity involved by PLL (to lower risk of graft rejection).

          -  Interferon- or tyrosine kinase-refractory CML in first chronic phase, TKI-intolerant
             CML in first chronic phase, or CML in second or subsequent chronic phase

          -  Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)

             o Intermediate-2 or High risk score by DIPSS Plus is required for a diagnosis of
             myelofibrosis

          -  Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment
             regimen, based on the International Myeloma Working Group (IMWG) criteria.49

          -  Hematologic malignancy in complete remission with minimal residual disease (MRD) non
             detectable OR detectable by conventional cytogenetics, FISH, flow cytometry, or
             molecular testing or hematologic malignancies in partial remission

        Donor eligibility

          -  Donors must be either:

          -  HLA-haploidentical or HLA-identical relatives of the patient based on allele or allele
             group level typing as defined in Section 4.1.

          -  Medically fit to and willing to donate

          -  Lack of recipient anti-donor HLA antibody

          -  Has not donated blood products to patient

        Exclusion Criteria:

          -  Any individual that does not meet the eligibility criteria for transplantation or
             donor eligibility will not be a part of this trial.