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Sponsors and Collaborators: |
National Institute of Allergy and Infectious Diseases (NIAID) Immune Tolerance Network |
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Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00288626 |
The purpose of this study is to determine the effectiveness of a new treatment for multiple sclerosis (MS), a serious disease in which the immune system attacks the brain and spinal cord. MS can be progressive and severe and lead to significant disability. The study treatment involves the use of high-dose chemotherapeutic drugs to suppress the immune system. The participant's own (autologous) blood-forming (hematopoietic, CD34+) stem cells are collected before the chemotherapy is given, and then transplanted back into the body following treatment. Transplantation of autologous hematopoietic stem cells is required to prevent very prolonged periods of low blood cell counts after the high-dose chemotherapy.
Condition | Intervention | Phase |
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Multiple Sclerosis |
Drug: Granulocyte-colony stimulating factor (G-CSF) and prednisone Drug: Carmustine, etoposide, cytarabine, and melphalan (BEAM) Procedure: Autologous hematopoietic stem cell transplant |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Phase II Study of High-Dose Immunosuppressive Therapy (HDIT) Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) and Thymoglobulin, and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) for the Treatment of Poor Prognosis Multiple Sclerosis |
Estimated Enrollment: | 30 |
Study Start Date: | July 2006 |
Estimated Study Completion Date: | January 2015 |
Estimated Primary Completion Date: | September 2014 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental |
Drug: Granulocyte-colony stimulating factor (G-CSF) and prednisone
Growth factor regimen; occurs at study entry
Drug: Carmustine, etoposide, cytarabine, and melphalan (BEAM)
High-dose chemotherapy; occurs seven or more days following collection of autologous graft
Procedure: Autologous hematopoietic stem cell transplant
Occurs after growth factor regimen and collection of autologous graft
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MS is a chronic autoimmune disease of the central nervous system in which myelin, the protective coat that surrounds nerve cells, is damaged or destroyed by autoimmune T cells and macrophages, leading to an eventual loss of neurologic function. In a pilot study in Europe using high-dose chemotherapy, it was observed that 18 of 19 MS patients stabilized or improved clinically, and only one patient showed a new lesion on magnetic resonance imaging (MRI) of the brain at 4.5 years after treatment. Improvement was seen in quality-of-life assessments.
In ITN033AI, high-dose chemotherapy with autologous CD34-selected hematopoietic cell transplantation will be given to confirm the results from the pilot study and to offer therapy to patients with early MS and a poor prognosis. Research studies will be performed in addition to clinical assessments to better understand the effect of the treatment on the activity of MS. High-dose chemotherapy will be used to deplete autoreactive immune cells. These regimens also deplete the bone marrow, the source of blood-forming CD34+ stem cells which causes very low blood counts. Therefore, the participant's autologous CD34+ hematopoietic stem cells will be collected before high dose immunosuppressive therapy is given and then returned as a transplant post-chemotherapy. Patients will be followed closely after the autologous transplantation since they will be at risk for infections after treatment.
At the beginning of the study, participants will undergo a number of screening and baseline procedures, including a physical exam, blood collection, MS-confirming neurology exams and questionnaires, and MRI procedures. Participants will be given prednisone and granulocyte-colony stimulating factor (G-CSF) to mobilize CD34+ hematopoietic stem cells from the bone marrow into the peripheral blood. When the peripheral blood CD34+ cell count reaches 20,000 cells/ml or greater, these cells will be collected by leukapheresis. In this process, a catheter is placed into a large blood vessel, peripheral blood is withdrawn, and a high speed sedimentation (leukapheresis) device is used to separate and retain the cells required for autologous transplantation. Other blood cells are then returned to the participant's body. In the laboratory, the CD34+ hematopoietic stem cell graft will be selected and prepared from the leukapheresis collection, and stored until needed for transplant. Seven or more days following the collection of their autologous graft, participants will be hospitalized and receive high-dose chemotherapy consisting of carmustine, etoposide, cytarabine, and melphalan (BEAM) and thymoglobulin. This is followed by transplantation of the autologous hematopoietic cell graft. Participants will remain in the hospital for observation during recovery of their peripheral blood cell counts, as described in the protocol. Participants will receive G-CSF and blood transfusions, if needed, and will be monitored for infections. Following discharge from the hospital, eight study visits will occur over sixty months (five years).
During these visits, participants will undergo blood and urine collection, MRI studies, leukapheresis, and MS neurology exams and will complete questionnaires.
Ages Eligible for Study: | 18 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Ohio | |
Ohio State University School of Medicine | Recruiting |
Columbus, Ohio, United States, 43210 | |
Contact: Lisa Hafer 614-293-7877 hafer.15@osu.edu | |
Principal Investigator: Michael K. Racke, MD | |
Principal Investigator: Steven M. Devine, MD | |
United States, Texas | |
M.D. Anderson Cancer Center; Transplant site, please contact Baylor College of Medicine | Recruiting |
Houston, Texas, United States, 77230-1402 | |
Contact: Uday Popat, MD 713-745-3055 upopat@mdanderson.org | |
Principal Investigator: Uday Popat, MD | |
Baylor College of Medicine | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Semahat Eiswirth, RN 713-798-6059 sparilti@bcm.edu | |
Contact: George J. Hutton, MD 713-798-8170 ghutton@bcm.tmc.edu | |
Principal Investigator: George J. Hutton, MD | |
United States, Washington | |
Fred Hutchinson Cancer Research Center | Recruiting |
Seattle, Washington, United States, 98109-1024 | |
Contact: Bernie McLaughlin, RN 206-667-4916 bmclaugh@fhcrc.org | |
Principal Investigator: James Bowen, MD | |
Principal Investigator: Richard Nash, MD | |
Principal Investigator: George H. Kraft, MD |
Study Chair: | Richard A. Nash, MD | Fred Hutchinson Cancer Research Center, Clinical Research Division, University of Washington |
Study Chair: | James D. Bowen, MD | Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington |
Study Chair: | George H. Kraft, MD | Departments of Neurology and Rehabilitation Medicine, University of Washington |
Study Chair: | George J. Hutton, MD | The Maxine Messinger Multiple Sclerosis Clinic, The Methodist Hospital, Baylor College of Medicine |
Study Chair: | Uday Popat, MD | Department of Blood and Marrow Transplantation, University of Texas, M.D. Anderson Cancer Center |
Study Chair: | Michael K. Racke, MD | Department of Neurology, Ohio State University Medical Center |
Study Chair: | Steven M. Devine, MD | Department of Hematology and Oncology, Ohio State University Medical Center |
Responsible Party: | DAIT/NIAID ( Associate Director, Clinical Research Program ) |
Study ID Numbers: | DAIT ITN033AI, DAIT SCMS2 |
Study First Received: | February 7, 2006 |
Last Updated: | March 3, 2009 |
ClinicalTrials.gov Identifier: | NCT00288626 History of Changes |
Health Authority: | United States: Food and Drug Administration |
Hematopoietic Stem Cell Transplantation Immunosuppressive Agents |
Antimetabolites Prednisone Melphalan Autoimmune Diseases Immunologic Factors Demyelinating Diseases Carmustine Sclerosis Antiviral Agents Immunosuppressive Agents |
Etoposide phosphate Multiple Sclerosis Demyelinating Autoimmune Diseases, CNS Mitogens Antineoplastic Agents, Alkylating Antineoplastic Agents, Phytogenic Alkylating Agents Etoposide Autoimmune Diseases of the Nervous System Cytarabine |
Antimetabolites Melphalan Anti-Infective Agents Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Immunologic Factors Antineoplastic Agents Physiological Effects of Drugs Pathologic Processes Multiple Sclerosis Therapeutic Uses Etoposide Alkylating Agents Cytarabine |
Autoimmune Diseases of the Nervous System Autoimmune Diseases Immune System Diseases Demyelinating Diseases Carmustine Nervous System Diseases Sclerosis Immunosuppressive Agents Antiviral Agents Pharmacologic Actions Myeloablative Agonists Demyelinating Autoimmune Diseases, CNS Antineoplastic Agents, Alkylating Antineoplastic Agents, Phytogenic |