Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis
Condition: Myelofibrosis
MeSH terms: Primary Myelofibrosis
Intervention: Fludarabine, Melphalan +/- ATG
Intervention description: Conditioning regimen for Allogenic Stem Cell Transplant:
Related Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily)
Unrelated Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily) ATG (Thymoglobulin®) days -3 to -1 (0.5 mg/kg IV on day -3 [given over 6 hours], and 2 mg/kg on days -2 and -1 [given over 4 hours])
Intervention MeSH terms: Fludarabine; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Myelofibrosis; Myeloproliferative disease; Stem Cell Transplant; Allogeneic Transplant; Conditioning Regimen; Reduced Intensity Regimen; Fludarabine; Melphalan; ATG

Summary:

      Stem cell transplantation is used to treat may types of diseases. There a 2 types of
      transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called
      mini-transplants.

      This study proposes to use a conditioning regimen for allogeneic transplantation along with a
      reduced intensity transplant. Conditioning regiment is the name for the combination of
      chemotherapy drugs that is given to patients before receiving a transplantation of donor stem
      cells. It is hoped that the regimen designed for this study proves to be less toxic and has
      an equal or better anticancer effect than the regimens that are normally used. The regimen
      being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This
      regimen has been studied in recipients of matched sibling transplants and in recipients of
      alternative donor stem cells in other hematologic malignancies. Those subjects, who receive
      stem cells from an unrelated donor, will also receive and additional drug called ATG or anti
      thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the
      recipient rejecting the transplant (graft).

      The purpose of this study is to observe if reduced intensity transplants can be used to allow
      engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this
      type of transplant is much less toxic than traditional bone marrow transplants. Reduced
      intensity transplants may be better tolerated by patients who may experience serious side
      effects from standard (very intense) stem cell transplant.

      The study has been recently amended to follow all subjects for survival.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with the following disease: Idiopathic myelofibrosis, or spent PV-, or
             ET-related myelofibrosis in chronic phase (<20% blast cells in the bone marrow) with
             Lille score >1 at any time, or platelet <100K.

          -  Age 18-65 years.

          -  ECOG performance status < 3.

          -  Life expectancy >3 months.

          -  Adequate cardiac function, normal LVEF ≥ 45% by MUGA or echocardiogram and adequate
             pulmonary function DLCO ≥ 50% of predicted.

          -  Serum creatinine < 1.1 x the upper limit of normal (ULN) or Creatinine Clearance >50
             ml/min.

          -  Serum bilirubin < 2.0 mg/dl, SGPT <2.5 x upper limit of normal

          -  No evidence of chronic active hepatitis or cirrhosis

          -  HIV-negative

          -  Patient is not pregnant

          -  Patient or guardian able to sign informed consent.

          -  Patients with >20% myeloblasts in the blood or marrow, extramedullary blast cell
             proliferation or large foci of blasts in bone marrow biopsy specimens are not
             eligible.

          -  Pretransplant splenectomy: MMM patients with variable degrees of splenomegaly, or
             splenectomized, are eligible to be enrolled. Any decision of having a patient
             splenectomized prior to transplant will be made in each center prior to enrolling the
             patient in the study.

          -  Patients should be off treatment with investigational for at least 4 weeks and have
             recovered from all toxicities.

        Exclusion Criteria:

          -  Pregnancy

          -  HIV positive

          -  > 20% myeloblasts in the peripheral blood or bone marrow

          -  LVEF < 45%

          -  DLCO < 50% of predicted

          -  ECOG performance status ≥ 3

          -  Chronic active hepatitis or cirrhosis

          -  Chronic renal insufficiency