Reduced Intensity Conditioning Transplant Using Haploidentical Donors
Condition: Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Myelofibrosis; CMML; Multiple Myeloma
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: Fludarabine; Melphalan; Cyclophosphamide; peripheral blood stem cell transplant
Intervention description: fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;; cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.
Intervention MeSH terms: Cyclophosphamide; Melphalan; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: CML; AML; MDS; ALL; CLL/CPL; HD; NHL; MPS; CMML; MM

Summary:

      This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from
      partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The
      primary objective of the study is to estimate the incidence of graft rejection and acute
      GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS,
      chronic GVHD and EFS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  No available matched related or unrelated donor, OR a matched related or unrelated
             donor will not be available in time frame necessary to perform potentially curative
             transplant

          -  Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have
             negative HLA cross-match in host vs. graft direction)

          -  Karnofsky status ≥70%

          -  One of the following high-risk malignancies:

               1. Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase,
                  resistant or intolerant to available tyrosine kinase inhibitors; Chronic
                  myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with
                  blast crisis that has entered into a second chronic phase following induction
                  chemotherapy

               2. Acute Myelogenous Leukemia in first or greater remission

               3. Myelodysplastic Syndrome at least one of the following: treatment-related;
                  monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0
                  or greater; neutropenia or cytopenia requiring transfusion not responding to
                  therapy; peripheral or BM blast count of <10%; CMML

               4. Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete
                  remission; first complete remission; marrow blasts <5%, but persistence of
                  minimal residual disease by flow cytometry, cytogenetics, or FISH

               5. Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease
                  that has either relapsed or failed to respond adequately to conventional-dose
                  therapy including purine analogs

               6. Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and
                  intermediate-grade/diffuse): previously treated disease that has either relapsed
                  or failed to respond adequately to conventional-dose therapy or autologous
                  transplantation

               7. Myeloproliferative diseases (myelofibrosis, CMML)

               8. Multiple Myeloma with relapse after a prior autologous transplant or eligible for
                  allogeneic HSCT based on other risk factors

        Exclusion Criteria:

          -  not be excluded on basis of sex, racial, or ethnic backgrounds

          -  poor cardiac function: left ventricular ejection fraction <40%

          -  poor pulmonary function: FEV1 and FVC <50% predicted

          -  poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary
             malignancy)

          -  poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated
             creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault
             formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x
             Serum creatinine (mg/dl)

          -  HIV-positive

          -  prior allogeneic transplant

          -  women of childbearing potential who currently are pregnant or who are not practicing
             adequate contraception

          -  any debilitating medical or psychiatric illness which would preclude their giving
             informed consent or their receiving optimal treatment and follow-up