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

NCT ID: NCT00004143

Last Updated: 2014-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-09-30
• Study Completion Date: 2009-06-30

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.

Conditions

Sickle Cell Anemia; Severe Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria (PNH); Pure Red Cell Aplasia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Campath SCT for hemoglobinopathies

Campath, Chemo and/or TBI Allo SCT

Group Type: EXPERIMENTAL

Campath, Chemo and/or TBI Allo SCT

Intervention Type: DRUG

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.

Campath SCT for Bone Marrow Failure

Campath, Chemo and/or TBI Allo SCT

Group Type: EXPERIMENTAL

Campath, Chemo and/or TBI Allo SCT

Intervention Type: DRUG

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.

Interventions

Campath, Chemo and/or TBI Allo SCT

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.

Intervention Type: DRUG

Other Intervention Names

Alemtuzumab; Allogeneic Hematopoietic Stem Cell Transplant

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 2.
• 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:

1. bilirubin and hepatic transaminases and creatinine must be reviewed by the transplantation center and deemed acceptable.

2. HIV antibody negative.

3. 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.

I) Hemoglobinopathies:

(a)Sickle Cell Anemia having history of one or more of the following despite treatment with standard therapies such as hydroxyurea: i) 2 or more episodes of acute chest syndrome since age 13 years ii) pulmonary hypertension as measured by tricuspid regurgitant jet velocity of greater than 2.5m/s iii) 2 or more painful crisis per year requiring medical care and analgesia in excess of what is needed at baseline.

iv) history of cerebrovascular accident (b)Thalassemia major: Those eligible will have either cardiac or hepatic sequela of thalassemia as documented by biopsy or functional studies. For those with hepatic damage, this would be an increase in size by 50% of the liver or a doubling of the total bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), or alkaline phosphatase. To be eligible for transplant due to cardiac damage, there must be evidence of left ventricular dysfunction as measured by MUGA scan or echocardiography.

II) Bone marrow failure Disorders

1. Severe Aplastic Anemia: Cytopenia consisting of at least 2 of the following 3: absolute neutrophil count less than 500/μL, platelet count less than 20,000/μL, and reticulocyte count less than 50,000/μL.

2. Paroxysmal nocturnal hemoglobinuria (PNH): Patients must have a history of either life-threatening thrombosis, cytopenia, transfusion dependence or recurrent, debilitating hemolytic crisis

3. Pure red cell aplasia: Patients must be transfusion dependent.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

David Rizzieri, MD

OTHER

Sponsor Role: lead

Responsible Party

David Rizzieri, MD

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David A. Rizzieri, MD

Role: STUDY_CHAIR

Duke Cancer Institute

Mitchell Horwitz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Florida Hospital Cancer Institute

Orlando, Florida, United States

Duke Cancer Institute

Durham, North Carolina, United States

Countries

United States

Other Identifiers

DUMC-1340-99-7

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-G99-1617

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CDR0000067374

Identifier Type: -

Identifier Source: secondary_id

Pro00008771

Identifier Type: -

Identifier Source: org_study_id