Saturday, October 07, 2006
This study is currently recruiting patients.
Verified by National Institute of Allergy and Infectious Diseases (NIAID) August 2006
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network
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
Drug: Granulocyte-colony stimulating factor (G-CSF)
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
Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):
Primary Outcomes: Time to treatment failure during the 5 years after transplant
Expected Total Enrollment: 30
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 - 60 Years, Genders Eligible for Study: Both
Diagnosis of relapsing-remitting or progressive-relapsing multiple sclerosis for less than 10 years using McDonald Criteria. More information on this criterion can be found in the protocol.
Score between 3.0 and 5.5 on the Expanded Disability Status Scale (EDSS)
T2 abnormalities on brain MRI consistent with MS
Two or more relapses in 12 months time on interferon (IFN), glatiramer acetate (GA), or mitoxantrone with EDSS increase greater than 0.5, maintained for greater than 3 months OR one relapse on IFN, GA, or mitoxantrone, together with MRI changes consistent with poor prognosis. More information on this criterion can be found in the protocol.
On IFN or GA for at least 6 months before the relapses occur that are counted to satisfy previous inclusion criterion OR have received at least 3 doses of mitoxantrone on a treatment schedule before the relapses occur that are counted to satisfy previous inclusion criterion
Approval by an MS Review Panel to participate in the study. More information on this criterion can be found in the protocol.
In good clinical condition with adequate organ function and without coexisting medical problems that would increase the risk to the participant
Willing to use acceptable methods of contraception
Willing and able to comply with all study requirements
Willing to accept and comprehend irreversible sterility as side effect of therapy
Primary progressive MS
Secondary progressive MS without relapses (i.e., progression without exacerbations or relapses) for 12 or more months
Neuromyelitis optica, a disease similar to MS
Initiation of new immunosuppressant treatment after the participant becomes eligible for the protocol or continuance of immunosuppressant drugs after the participant is screened for the protocol. Treatment with IFN, GA, or corticosteroids is permitted after the participant becomes eligible for the protocol.
Lapse of greater than 4 months between the time a participant is eligible for the protocol and initiation of protocol treatment except when judged acceptable by the MS Review Panel
Prior treatment with investigational immunosuppressive agents within 3 months of study eligibility
Prior treatment with natalizumab
History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)
Active hepatitis B or C infection, cirrhosis, or HIV infection
Uncontrolled diabetes mellitus
Uncontrolled viral, fungal, or bacterial infection. Patients with asymptomatic bacteriuria are not excluded.
Any illness that would jeopardize the ability to tolerate aggressive chemotherapy
Prior history of malignancy, except localized basal cell or squamous skin cancer. Other malignancies for which the subject is judged cured by the administered therapy will be considered on an individual basis.
Hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins or to iron compounds/medications
Metallic objects implanted in the body that would affect MRI exams
Psychiatric illness, mental deficiency, or cognitive dysfunction
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00288626
City of Hope National Medical Center, Duarte, California, 91010, United States; Recruiting
Emily Krupka, RN, BSN 626-256-4673 Ext. 64658 firstname.lastname@example.org
Stephen J. Forman, MD, Principal Investigator
Harry Openshaw, MD, Principal Investigator
University of Texas - Southwestern, Dallas, Texas, 75390-9036, United States; Not yet recruiting
Olaf Stuve, MD 214-648-2330 email@example.com
Olaf Stuve, MD, Principal Investigator
M.D. Anderson Cancer Center, Houston, Texas, 77230-1402, United States; Not yet recruiting
Marilyn S. Davis, RN, CCRC 713-745-4371 firstname.lastname@example.org
Uday Popat, MD, Principal Investigator
Baylor College of Medicine, Houston, Texas, 77030, United States; Not yet recruiting
George J. Hutton, MD 713-798-8170 email@example.com
George J. Hutton, MD, Principal Investigator
Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109-1024, United States; Recruiting
Bernie McLaughlin, RN 206-667-4916 firstname.lastname@example.org
James Bowen, MD, Principal Investigator
Richard Nash, MD, Principal Investigator
Study chairs or principal investigators
Richard A. Nash, MD, Study Chair, Fred Hutchinson Cancer Research Center, Clinical Research Division, University of Washington
Harry Openshaw, MD, Study Chair, Department of Neurology, City of Hope National Medical Center
Stephen J. Forman, MD, Study Chair, Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center
James D. Bowen, MD, Study Chair, Department of Neurology, University of Washington
George J. Hutton, MD, Study Chair, The Maxine Messinger MS Clinic, The Methodist Hospital, Baylor College of Medicine
Uday Popat, MD, Study Chair, Department of Blood and Marrow Transplantation, University of Texas, M.D. Anderson Cancer Center
Olaf Stuve, MD, Study Chair, Department of Neurology, Center for Immunology, University of Texas Southwestern Medical School
Click here for the Immune Tolerance Network Web site
Fassas A, Nash R. Stem cell transplantation for autoimmune disorders. Multiple sclerosis. Best Pract Res Clin Haematol. 2004 Jun;17(2):247-62. Review.
Muraro PA, Douek DC. Renewing the T cell repertoire to arrest autoimmune aggression. Trends Immunol. 2006 Jan 4; [Epub ahead of print]
Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, Campbell C, Memon S, Nagle JW, Hakim FT, Gress RE, McFarland HF, Burt RK, Martin R. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med. 2005 Mar 7;201(5):805-16. Epub 2005 Feb 28.
Saccardi R, Mancardi GL, Solari A, Bosi A, Bruzzi P, Di Bartolomeo P, Donelli A, Filippi M, Guerrasio A, Gualandi F, La Nasa G, Murialdo A, Pagliai F, Papineschi F, Scappini B, Marmont AM. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood. 2005 Mar 15;105(6):2601-7. Epub 2004 Nov 16.
Tyndall A, Saccardi R. Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions. Clin Exp Immunol. 2005 Jul;141(1):1-9. Review.
Study ID Numbers: DAIT ITN033AI; DAIT SCMS2
Last Updated: August 3, 2006
Record first received: February 7, 2006
ClinicalTrials.gov Identifier: NCT00288626
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-10-06