Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes
Overview
- Phase
- Phase 2
- Intervention
- Campath, Chemo and/or TBI Allo SCT
- Conditions
- Sickle Cell Anemia
- Sponsor
- David Rizzieri, MD
- Enrollment
- 2
- Locations
- 2
- Primary Endpoint
- Number of Patients With Neutrophil Engraftment
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
David Rizzieri, MD
MD
Duke University
Eligibility Criteria
Inclusion Criteria
- •Patients must have their clinical material reviewed at the transplanting institution and the diagnosis confirmed
- •Performance status must be Cancer and Leukemia Group B (CALGB) Performance Status (PS) 0, 1, or
- •Patients must have a 5/6 to 6/6 HLA matched family member donor who is evaluated and deemed able to provide PBSCs and/or marrow by the transplant team. Donor must have \< 50% Hemoglobin S (HgS) on hemoglobin electrophoresis. Cytomegalovirus (CMV) status of the donor will be assessed, but not used as an exclusion criterion.
- •Patients must meet the following laboratory parameters unless due to disease status as determined by the treating physician:
- •bilirubin and hepatic transaminases and creatinine must be reviewed by the transplantation center and deemed acceptable.
- •HIV antibody negative.
- •hematocrit, white cell count, platelet counts and hematologic status will be reviewed by the treating physician before patient is deemed acceptable.
- •Patient must agree to use some form of adequate birth control during the periods that they receive chemotherapy and any post-chemotherapy medications related to the transplant.
- •Patients must also have a resting multiple gated acquisition scan (MUGA) or echocardiogram and Pulmonary Function Tests (PFTs) with Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) performed before transplant. Recommended minimum standards include an Ejection Fraction (EF) greater than 40% and DLCO greater than 40% for this less toxic regimen.
- •Appropriate cardiology or pulmonary consultations should be considered if the patient has severe cardiac or lung disease at the initiation of therapy.
Exclusion Criteria
- •pregnant or lactating women,
- •patients with other major medical or psychiatric illnesses which the treating or transplant physician feels could seriously compromise compliance to this protocol
- •patients with known history of allergies to murine protein
Arms & Interventions
Campath SCT for hemoglobinopathies
Campath, Chemo and/or TBI Allo SCT
Intervention: Campath, Chemo and/or TBI Allo SCT
Campath SCT for Bone Marrow Failure
Campath, Chemo and/or TBI Allo SCT
Intervention: Campath, Chemo and/or TBI Allo SCT
Outcomes
Primary Outcomes
Number of Patients With Neutrophil Engraftment
Time Frame: 1 year post transplant
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).
Number of Patients With Platelet Engraftment
Time Frame: 1 year post transplant
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).
Number of Patients With Grade 3-4 Acute Graft Versus Host Disease (GVHD)
Time Frame: 60 days post transplant
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.
Number of Participants With Grade 3-4 Unexpected Adverse Events
Time Frame: 45 days post transplant
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.
Number of Participants With Transplant-related Mortality
Time Frame: 100 days
Number of patients who died due to transplant-related complications
Secondary Outcomes
- Overall Survival(2 years)