RATIONALE: Although used primarily to treat malignant disorders of the blood, allogeneic stem cell transplantation can also cure a variety of non-cancerous, inherited or acquired disorders of the blood. Unfortunately, the conventional approach to allogeneic stem cell transplantation is a risky procedure. For some non-cancerous conditions, the risks of this procedure outweigh the potential benefits. This protocol is designed to test a new approach to allogeneic stem cell transplantation. It is hoped that this approach will be better suited for patients with non-cancerous blood and bone marrow disorders.
OBJECTIVES: Primary Objective(s): 1. Evaluate the feasibility in terms of mortality, occurrence of acute graft versus host disease, and grades 3-4/4 toxicity of in vivo and in vitro Campath coupled with concomitantly administered nonmyeloablative fludarabine, cyclophosphamide and total body irradiation (TBI) followed by Human Leukocyte Antigen (HLA) 5-6/6 matched family member allo peripheral blood stem cell transplant (PBSCT). 2. Evaluate the engraftment rate of HLA 5-6/6 matched family member patients who receive in vivo Campath followed by concomitantly administered fludarabine, cyclophosphamide and total body irradiation (TBI) as a conditioning regimen with Campath-treated peripheral blood stem cells (in vitro and in vivo exposure). Secondary Objective(s): 1. Evaluate the response rate and survival of patients who receive a non-myeloablative conditioning regimen of in vivo Campath followed by concomitantly administered fludarabine, cyclophosphamide and total body irradiation (TBI) with Campath-treated peripheral blood stem cells. 2. Evaluate the recovery of immune function post engraftment with this regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Allogeneic PBSC/marrow will be collected/harvested from the donor after granulocyte colony-stimulating factor (G-CSF) priming. The allogeneic PBSCs will be infused as per current institutional practice.
Florida Hospital Cancer Institute
Orlando, Florida, United States
Duke Cancer Institute
Durham, North Carolina, United States
Number of Patients With Neutrophil Engraftment
Number of patients with neutrophil engraftment: Absolute Neutrophil Count (ANC) \> 500/μL and hemoglobin level remaining above 10 g/dL without transfusion support, with tests showing at least 2.5% donor cells present. Primary graft failure is defined as absence of establishment of adequate donor hematopoiesis by day 42 with bone marrow cellularity \< 5%, peripheral White Blood Count (WBC) \< 500/μL, peripheral ANC \< 100/μL, and/or platelets \< 10,000/μL by day 120 with absence of megakaryocytes in the bone marrow (in the absence of disease relapse).
Time frame: 1 year post transplant
Number of Patients With Platelet Engraftment
Number of patients with platelet engraftment - Platelets \> 20,000/μL and hemoglobin level remaining above 10 g/dL without transfusion support, with tests showing at least 2.5% donor cells present. Primary graft failure is defined as absence of establishment of adequate donor hematopoiesis by day 42 with bone marrow cellularity \< 5%, peripheral White Blood Count (WBC) \< 500/μL, peripheral ANC \< 100/μL, and/or platelets \< 10,000/μL by day 120 with absence of megakaryocytes in the bone marrow (in the absence of disease relapse).
Time frame: 1 year post transplant
Number of Patients With Grade 3-4 Acute Graft Versus Host Disease (GVHD)
Number of patients with Grade 3-4 acute Graft Versus Host Disease (GVHD). GVHD will be monitored at least two times per week through day 45, then weekly through day 60 and graded by 2 persons at each institution, to ensure internal consistency in grading.
Time frame: 60 days post transplant
Number of Participants With Grade 3-4 Unexpected Adverse Events
An unexpected adverse event is one that differs in the nature, severity, or frequency from (a) the research procedures that are described in the protocol-related documents, (such as the IRB-approved research protocol and informed consent document) as expected, and/or (b) the characteristics of the subject population being studied.
Time frame: 45 days post transplant
Number of Participants With Transplant-related Mortality
Number of patients who died due to transplant-related complications
Time frame: 100 days
Overall Survival
Number of patients alive 2 years after transplant
Time frame: 2 years
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