Clinical Trial: Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes

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 Summary:

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.

Sponsor: David Rizzieri, MD

Current Primary Outcome:

  • 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 e

    Original Primary Outcome:

    Current Secondary Outcome: Overall Survival [ Time Frame: 2 years ]

    Number of patients alive 2 years after transplant


    Original Secondary Outcome:

    Information By: Duke University

    Dates:
    Date Received: December 10, 1999
    Date Started: September 1999
    Date Completion:
    Last Updated: November 19, 2014
    Last Verified: November 2014