Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant
Condition: Hodgkin's Disease; Non Hodgkin's Lymphoma; Myeloma; Leukemia; Myelodysplasia
MeSH terms: Hodgkin Disease; Preleukemia; Myelodysplastic Syndromes
Intervention: Non-myeloablative Stem Cell Transplantation
Intervention description: The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. Group B's prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 264.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stem Cell Transplantation, Non-myeloablative

Summary:

      The central hypothesis of this study is that use of a less toxic chemotherapy preparative
      regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell
      depletion with alemtuzumab for patients with high risk hematologic malignancies will allow
      effective control of disease and improved disease free and overall survival compared with
      historical expectations. Specifically, the objectives are to estimate toxicity, disease free,
      progression free, event free, and overall survival rates in patients treated with alemtuzumab
      T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic
      transplantation; evaluate immune recovery following this reduced intensity allogeneic
      immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.
    

Eligibility criteria:

        Recipient Inclusion Criteria:

          -  Subjects must have their diagnosis confirmed at the transplant center.

          -  Performance status must be Cancer and Leukemia Group B (CALGB) = 0, 1, or 2.

          -  Subjects must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8
             or better allele level match matched unrelated donor (MUD) (at A,B, C, DRB1, DQ).

          -  HIV negative.

          -  Women of child bearing potential must have a negative pregnancy test within 1 week of
             starting therapy.

          -  Subjects > or equal to 18 years of age are eligible.

          -  Subjects must have a Multi Gated Acquisition Scan (MUGA) and/or Echocardiography
             (ECHO) or cardiac magnetic resonance (MR) and or diffusing capacity testing of the
             lung for carbon monoxide (DLCO) performed before transplant.

          -  Specific populations:

               -  Group A) Subjects with a high chance of progressive lymphoid or myelomatous
                  diseases.

               -  Group B) Subjects with a high chance of progressive myeloid diseases, marrow
                  failure syndromes or myeloproliferative disorders

        Recipient Exclusion Criteria:

          -  Pregnant or lactating women.

          -  Subjects with other major medical or psychiatric illnesses which the treating
             physician feels could seriously compromise tolerance to this protocol.

          -  Subjects with uncontrolled, progressive infections.

          -  Subjects who are good candidates for long term disease control with standard
             chemotherapy or radiation or high dose therapy and autologous support.

          -  Subjects with active central nervous system (CNS) disease.

        Donor Inclusion Criteria:

          1. Donor must be capable of providing informed consent. If 14-17 years of age, a 'single
             patient exemption' from the local Institutional Review Board must be obtained.

          2. Donor must not have any medical condition which would make mobilization or apheresis
             more than a minimal risk, and should have the following:

               1. Adequate cardiac function by history and physical examination. Those with a
                  history of cardiac failure or infarction should be evaluated by a cardiologist
                  prior to donation

               2. Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of
                  3000, and platelets 100,000.

          3. Females should not be pregnant or lactating and have a negative serum pregnancy test
             within 1 week of beginning mobilization if of child bearing potential.