Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath
Condition: Lymphoma; Myeloma; Leukemia; Myelodysplasia; Solid Tumors
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Campath Purged Non-myeloablative ASCT; Donor Apheresis
Intervention description: Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.; Donor will receive Granulocyte colony-stimulating factor (G-CSF) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). Granulocyte-macrophage colony-stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneous or similar growth factor for donor mobilization. Donors will receive at least 3-6 doses of daily growth factor until adequate cells are mobilized.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 176.0
Sex: All
Minimum age: 17 Years
Healthy volunteers: No
Keywords: Allogeneic Stem Cell Transplantation, Campath, HLA-Matched

Summary:

      Allogeneic transplantation is used to treat many malignant and non-malignant diseases, though
      the potential toxicities of the procedure remain high. We and others have shown that a less
      toxic preparative regimen allows reliable allogeneic engraftment for allogeneic
      transplantation.

      The primary purpose of this treatment trial is to follow patients undergoing allogeneic
      transplantation for long term outcomes. The regimen used has been tested in our prior phase I
      / II trial which has completed accrual. The issues of engraftment and rate of graft versus
      host disease have been answered and our success has led to this regimen being a standard
      approach for less toxic allogeneic therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have their pathology reviewed and the diagnosis confirmed.

          -  Performance status (PS) must be Cancer and Leukemia Group B (CALGB) PS 0, 1, or 2

          -  Patients must have a 3-5/6 Human leukocyte antigen (HLA)-matched related donor who is
             evaluated and deemed able to provide peripheral blood progenitor cells (PBPCs) and/or
             marrow by the transplant team.

          -  HIV antibody negative.

          -  Patients must test negative for serum beta-human chorionic gonadotropin (hCG) and must
             agree to use some form of adequate birth control during the periods they receive
             chemotherapy and any post-chemotherapy medications related to the transplant.

          -  Patients must be 17 years of age or greater.

          -  Patients must also have a resting Multi Gated Acquisition Scan (MUGA) and/or
             echocardiography (ECHO) and pulmonary function tests (PFTs) with testing of diffusing
             capacity of the lung for carbon monoxide (DLCO) performed before transplant and found
             to be acceptable according to the treating institution's guidelines. The required
             minimum standards include MUGA and/or ECHO showing an ejection fraction (EF) of 40%
             and PFTs showing DLCO of 40%. Those with an EF 40-50%, undergo cardiac evaluation and
             consultation. Also, those with DLCO 40-50%, undergo pulmonary evaluation and
             consultation.

          -  Specific populations for each disease category:

               -  Hematologic malignancies Those with high risk or relapsed hematologic malignancy
                  (including myeloid and lymphoid leukemias and lymphomas, myeloma or myelomatous
                  like diseases, myeloproliferative disease, myelodysplasia). Those with good risk
                  disease (first remission acute myeloid leukemia (AML) with myelomonocytic
                  together with bone marrow eosinophilia (M4eos) - inversions in chromosome 16,
                  promyelocytic (M3) AML with translocations in chromosomes (15;17); or
                  translocations in chromosomes (8;21) in first remission are not eligible).

               -  Bone marrow failure:

                    -  Those specifically with idiopathic or secondary moderate, severe or very
                       severe aplastic anemia (idiopathic or secondary) according to the accepted
                       'Camitta criteria' would be candidates.

                    -  Those with diseases known to lead to severe marrow failure are eligible as
                       well. These include those with myelofibrosis or Paroxysmal nocturnal
                       hemoglobinuria (PNH).

               -  Solid Tumors:

                    -  Patients must have had a biopsy confirming disease recurrence (metastases)
                       at some point in their history, unless the patient presented with metastatic
                       disease, in which case the initial primary site biopsy is adequate.

          -  Patients with renal cell cancer, or melanoma will be eligible for this approach at
             this time. Patients will have had documented metastatic disease at some time in the
             past. Patients who are in remission or with residual disease after prior therapy for
             their metastatic disease are eligible, as there is no accepted cure for these patients
             with metastatic disease.

          -  Breast Cancer- Patients will have had documented metastatic disease at some time in
             the past. Patients who are in remission or with residual disease after prior therapy
             for their metastatic disease are eligible. Patient must have failed at least one
             chemotherapy regimen for their metastatic disease and 1 hormonal agent if they are
             receptor positive.

        Exclusion Criteria:

          -  Pregnant or lactating women,

          -  Patients with other major medical or psychiatric illnesses which the treating
             physician feels could seriously compromise tolerance to this protocol, and

          -  Leukemia patients in first remission with good risk cytogenetics for leukemia
             [t(15;17); t(8,22)]