- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00004143
Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes
Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary Objective(s):
- 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).
- 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):
- 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.
- Evaluate the recovery of immune function post engraftment with this regimen.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Florida
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Orlando, Florida, United States, 32804
- Florida Hospital Cancer Institute
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- 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.
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
- 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.
- Paroxysmal nocturnal hemoglobinuria (PNH): Patients must have a history of either life-threatening thrombosis, cytopenia, transfusion dependence or recurrent, debilitating hemolytic crisis
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Campath SCT for hemoglobinopathies
Campath, Chemo and/or TBI Allo SCT
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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.
Other Names:
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EXPERIMENTAL: Campath SCT for Bone Marrow Failure
Campath, Chemo and/or TBI Allo SCT
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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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Neutrophil Engraftment
Time Frame: 1 year post transplant
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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).
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1 year post transplant
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Number of Patients With Platelet Engraftment
Time Frame: 1 year post transplant
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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).
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1 year post transplant
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Number of Patients With Grade 3-4 Acute Graft Versus Host Disease (GVHD)
Time Frame: 60 days post transplant
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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.
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60 days post transplant
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Number of Participants With Grade 3-4 Unexpected Adverse Events
Time Frame: 45 days post transplant
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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.
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45 days post transplant
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Number of Participants With Transplant-related Mortality
Time Frame: 100 days
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Number of patients who died due to transplant-related complications
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100 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 2 years
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Number of patients alive 2 years after transplant
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2 years
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: David A. Rizzieri, MD, Duke Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Urologic Diseases
- Urological Manifestations
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Urination Disorders
- Proteinuria
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Myelodysplastic Syndromes
- Anemia
- Anemia, Sickle Cell
- Anemia, Aplastic
- Red-Cell Aplasia, Pure
- Hemoglobinopathies
- Bone Marrow Failure Disorders
- Pancytopenia
- Hemoglobinuria
- Hemoglobinuria, Paroxysmal
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Alemtuzumab
Other Study ID Numbers
- Pro00008771
- DUMC-1340-99-7 (OTHER: Duke University Medical Center Institutional Review Board)
- NCI-G99-1617 (OTHER_GRANT: National Cancer Institute)
- CDR0000067374
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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