Allo Non-myeloablative SCT Utilizing Matched Family Member Stem Cells Purged Using Campath
Allo Non-myeloablative SCT Utilizing Matched Family Member Stem Cells Purged Using Campath
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 subjects 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.
Allogeneic bone marrow transplantation may cure or ameliorate illnesses of many types;
 however the toxicity of the procedure limits its broad applicability. Hematologic
 malignancies of all types have shown responses. Those with marrow failure, such as aplasia,
 and hemoglobinopathies have further shown responses in multiple trials as well. Even patients
 with certain solid tumors, such as breast, renal cell, and melanoma have shown partial or
 complete responses to allogeneic therapy. The limiting effect of the historical methods of
 aggressive induction for allogeneic therapy were extremely toxic, requiring limiting those
 offered allogeneic therapy to the healthiest of the ill patients. Work over the last decade
 has shown that less toxic agents targeting the immune system effectively allowed engraftment
 with less effects on the patient's liver, lungs, and other vital organs. We and others have
 completed multiple trials showing the effective use of these less toxic, non-myeloablative,
 regimens for allogeneic therapy. Trials with fludarabine and cyclophosphamide at standard
 doses (patients are not ablated and recover blood counts in 2 weeks) allow for 80% of
 patients to engraft donor cells. Some groups have added low doses of radiation to this
 combination, with 80-100% allogeneic engraftment. The lessened toxicity of this approach has
 been confirmed in multiple studies, including our own data with the specific schema in this
 treatment plan reviewed below. Phase I results with this combination: Our group has combined
 the above combination of fludarabine and cyclophosphamide with the antibody CAMPATH 1H. This
 antibody is given to the patient to purge the immune system and prevent rejection. It also
 purges the T cells in the donated stem cells to minimize graft versus host disease (GVHD).
 This approach has been proven successful in multiple trials using standard more toxic
 ablative procedures. Our approach over the last 3 years has been very successful using this
 antibody with the less toxic non-myeloablative procedure and our trials have completed. We
 have presented our preliminary results, with data on long term follow up for outcomes being
 collected. We have shown that 100% of patients with a malignancy or marrow failure treated
 with this regimen in our early phase trial engrafted donor cells. There was only an 8% severe
 GVHD risk, though the risk for infection remains high with a risk of fungal and viral
 infection about 5% each. Despite working with older, more infirmed patients, only 3/40
 patients died within the first 100 days from therapy. Similar approaches on matched unrelated
 donors have been reported by other groups as well. As the phase I feasibility trial is
 complete and the outcomes encouraging, this protocol will follow the same general treatment
 plan and allow further information to be gained for long term follow up of subjects treated
 with this approach.
Inclusion Criteria:

 -  Subjects must have their pathology reviewed and the diagnosis confirmed.

 -  Performance status must be Cancer and Leukemia Group B (CALGB) performance score 0, 1,
 or 2

 -  Subjects must have a 6/6 Human leukocyte antigen (HLA)-matched related donor who is
 evaluated and deemed able to provide peripheral blood progenitor cells (PBPC) and/or
 marrow by the transplant team.

 -  HIV antibody negative.

 -  Subjects must test negative 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.

 -  Subjects must be >/=17 years of age

 -  Subjects must also have a resting multigated acquisition (MUGA) and/or ECHO and
 pulmonary function test (PFT) with diffusion capacity of lung (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:

 A) 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 inv 16 M4 Eos, M3 AML with t(15;17); or t(8;21)
 in first remission are not eligible).

 B) Bone marrow failure

 1. 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.

 2. Those with diseases known to lead to severe marrow failure are eligible as well. These
 include those with myelofibrosis or paroxysmal nocturnal hemoglobinuria (PNH).

 C) Solid Tumors Subjects 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.

 1. Subjects with renal cell cancer, or melanoma will be eligible for this approach at
 this time. Subjects will have had documented metastatic disease at some time in the
 past. Subjects 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.

 2. Breast Cancer- Subjects will have had documented metastatic disease at some time in
 the past. Subjects who are in remission or with residual disease after prior therapy
 for their metastatic disease are eligible. Subjects must have failed at least one
 chemotherapy regimen for their metastatic disease and 1 hormonal agent if they are
 receptor positive.

 Exclusion Criteria:

 1. pregnant or lactating women,

 2. patients with other major medical or psychiatric illnesses which the treating
 physician feels could seriously compromise tolerance to this protocol, and

 3. Leukemia patients in first remission with good risk cytogenetics for leukemia
 [t(15;17); t(8,22)]