Flu,Alemtuzumab,and TBI Followed By Donor Stem Cell Chronic Phase CML
Condition: Leukemia
MeSH terms: Leukemia
Intervention: Campath; Fludarabine; Total Body Irradiation (TBI); T-Cell Deplete
Intervention description: 30 mg on day -8 over 5-6 hours; Fludarabine 30 mg/m^2 on day -4 through day -2; Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0; Stem cells will be T cell depleted and given on day 0
Intervention MeSH terms: Fludarabine; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 4 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia

Summary:

      RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation
      (TBI) before a donor stem cell transplant helps stop the growth of cancer cells. It also
      stops the patient's immune system from rejecting the donor's stem cells. The donated stem
      cells may replace the patient's immune system and help destroy any remaining cancer cells
      (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
      infusion) that have been treated in the laboratory after the transplant may help increase
      this effect. Sometimes the transplanted cells from a donor can also make an immune response
      against the body's normal cells. Giving cyclosporine and alemtuzumab, and removing the T
      lymphocyte cells(T cells) from the donor cells before transplant, may stop this from
      happening.

      PURPOSE: This clinical trial is studying how well giving fludarabine, alemtuzumab, and
      total-body irradiation together with donor stem cell transplant and donor white blood cell
      (WBC) infusion works in treating patients with chronic phase chronic myelogenous leukemia
      (CML) that did not respond to previous imatinib mesylate.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients aged 4-75 with chronic myelogenous leukemia (CML) treatable by allogeneic
             hematopoietic stem cell transplant.

          -  Patients with cytogenetically confirmed chronic phase CML.

             o Hematologic parameters for chronic phase are: i) Percentage of blasts in peripheral
             blood or marrow < 15% ii) Percentage of blasts + promyelocytes in the peripheral blood
             or bone marrow < 30% iii) Percentage of basophils in blood or marrow <20% iv) Platelet
             count > 100 x 109/l

          -  Patients must have demonstrated refractoriness/resistance to STI571 defined as
             follows:

             i) Hematologically resistant- failure to achieve a complete hematologic remission
             (CHR) despite 3 months of STI571 therapy.

        ii) Hematologically refractory - a rising WBC count > 20 x 109/l confirmed by two samples
        taken two weeks apart in a patient with a previous CHR despite concurrent treatment with
        STI571 iii) Cytogenetically resistant - bone marrow cytogenetics showing > 65% Philadelphia
        chromosome positivity (Ph+) after 6 months of STI571 based therapy.

        iv) Cytogenetically refractory - An increase in the number of Philadelphia chromosome
        positive (Ph+) bone marrow cells by at least 30%, or an increase to > 65%, confirmed by
        samples at least 1 month apart following a previous STI571 induced cytogenetic response,
        while continuing STI571 therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          -  Patients with a human leukocyte antigen (HLA) matched sibling donor at the HLA-A, B,
             and DR loci.

          -  Patients with an unrelated hematopoietic stem cell donor must be matched using high
             resolution typing for class II human leukocyte antigen (HLA-DR beta-1, 3, 4, 5 and DQ
             beta-1) and matched with intermediate to high resolution molecular typing at class I
             human leukocyte antigen (HLA-A, B, and C) loci.

          -  Patients with accelerated or blast crisis of CML who have returned to chronic phase as
             described above are eligible.

          -  Written informed, voluntary consent.

        Exclusion criteria:

          -  Patients who have received another investigational drug within 30 days.

          -  Fertile men unwilling to use contraceptive techniques during and for 24 months
             following treatment.

          -  Females who are pregnant or fertile women unwilling to use contraceptive techniques
             for two months prior to entering the study and for 24 months following treatment.

          -  Patients with active bacterial or fungal infections unresponsive to medical therapy.

          -  Patients with organ dysfunction including cardiac ejection fraction of less than 35%
             or pulmonary status with a diffusing capacity of the lung for carbon monoxide(DLCO) of
             less than 40% and/or receiving supplemental oxygen.

          -  Liver Function Abnormalities: patients will be excluded if they are found to have
             fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension,
             alcoholic hepatitis, varices, history of bleeding varices, hepatic encephalopathy or
             chronic viral hepatitis where the total serum bilirubin is greater than 3 mg per
             deciliter with symptomatic biliary disease.

          -  Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable.

          -  Patients with a history of any prior bone marrow or peripheral blood stem cell
             transplantation.

          -  Patients with any other serious, uncontrolled, concomitant medical condition

          -  HIV positive patients

        Eligibility criteria for donors:

        Inclusion Criteria for Donors:

          -  Sibling donors are permitted if matched at class I human leukocyte antigen (HLA-A, B),
             and class II human leukocyte antigen (DR) loci.

          -  Unrelated donors must be matched for class II human leukocyte antigen(HLA-DR
             beta-1,2,3,4,5) and class II human leukocyte antigen (DQ beta-1) with high resolution
             typing and with intermediate resolution molecular typing at class I human leukocyte
             antigen(HLA-A, B, and C) loci.

          -  Donors must be eligible to serve as a peripheral stem cell allograft donor. Bone
             marrow donors will not be permitted on this protocol.

          -  Donors must be >18 and < 75 years of age.

        Exclusions Criteria for Donors:

          -  Volunteer donors who wish to serve as bone marrow donors only and refuse exogenous
             cytokines.

          -  Donors who are Human immunodeficiency virus (HIV+), Human T-lymphotropic virus
             (HTLV-1+), or hepatitis Bs Ag+..

          -  Donors with medical conditions that would result in increased risk for Granulocyte
             colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem
             cells (PBSC) including renal insufficiency with Cr > 2.0, idiopathic splenomegaly,
             underlying coagulopathy, uncontrolled coronary artery disease, and major surgery
             within 28 days.