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Study Summary
No. 2006-0018:.......Other Studies......Uday Popat......Stem Cell Transplantation and Cellular Therapy
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Study Summary Title
Study Summary
Number:
2006-0018
Study Title:A Phase II Study of High-Dose Immunosuppressive Therapy (HDIT) Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) + Thymoglobulin, and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) for the Treatment of Poor Prognosis Multiple Sclerosis
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Physician New Patient Referral
Name:Uday PopatPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Stem Cell Transplantation and Cellular TherapyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-745-3055
Contact us about clinical trials
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General Information
Disease Group:Other StudiesSupported By:N/A
Phase of Study:Phase IIReturn
Visit:
Weekly for 100 days after transplant. 3 monthly thereafter.
Treatment
Agents:
Antithymocyte Globulin
Autologous CD34+ Hematopoietic Progenitor Cells
Carmustine
Cytarabine
Etoposide
Melphalan
Home Care:None
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
30 days
Description/
Intervention:
The goal of the screening portion of this study is to evaluate your disease
condition and find out if you are eligible to take part in the main study. The
screening evaluation in some cases may change your diagnosis, or confirm the
diagnosis you have previously received. Specific testing on organs such as
your lungs, heart, and brain will be done to confirm that you do not have any
medical abnormalities that would increase your risk from the transplant.
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Study Objectives / Outcomes
Primary Objective:
  • To determine the 5-year durability of disease stabilization in Multiple Sclerosis (MS) subjects after HDIT and autologous HCT.
Secondary Objectives:
  • To evaluate the safety and efficacy of autologous HCT.
Tertiary Objectives:
  • To evaluate myelin content and axonal integrity using magnetic resonance imaging (MRI) approaches in MS subjects undergoing autologous HCT. Immune reconstitution and mechanisms of disease following autologous HCT for MS will also be explored through a number of specific endpoints.
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Study Status Information
Study Activation / Registration Date:05/15/2007
IRB Review and Approval Date:05/15/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:25
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Age between 18 and 60 years, inclusive.

2) Diagnosis of MS using McDonald Criteria.

3) MS duration < 15 yrs from diagnosis.

4) Relapsing remitting multiple sclerosis or progressive relapsing multiple sclerosis.

5) Extended Disability Status Scale (EDSS) 3.0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not taken into considertion in determinng EDSS for protocol eligibility).

6) T2 abnormalities on brain MRI consistent with MS.

7) Two or more relapses in 18 months or less on IFN, GA, natalizumab, or cytotoxic therapy with EDSS increase of 1.0 or greater for subjects with EDSS at screening of 3.0 – 3.5 (0.5 or greater for subjects with EDSS at screening of 4.0 – 5.5) sustained at least 4 weeks after at least one of these relapses. The EDSS increase is relative to the EDSS prior to the first relapse that is counted to establish eligibility. The increase may occur all at one of the two relapses or the increase may be cumulative over the < 18 months. OR Two or more relapses in 18 months or less "off therapy" but

8) having previously satisfied criterion 7a less than 4 years ago (dating from the first counted relapse on therapy that would satisfy 7a) with EDSS increase of 1.0 or greater for subjects with EDSS at screening of 3.0 – 3.5 (0.5 or greater for subjects with EDSS at screening of 4.0 – 5.5) sustained at least 4 weeks after at least one of the relapses in the < 18 months "off therapy." The EDSS increase is relative to the EDSS prior to the counted relapse in the < 18 months "off therapy." The increase may occur all at one of two relapses or increase may be cumulative over < 18 months "off therapy."

9) By "off therapy" is meant either (i) no therapy at all given in the < 18 months when the two relapses are experienced to establish eligibility or (ii) therapy has been given for part but not all of the < 18 months and that one of the two relapses in the < 18 months could have occurred while the patient was on therapy (or at a time when the therapy would be considered to be actve). OR: c. One relapse on IFN, GA, natalizumab or cytotoxic therapy with EDSS increase of 1.5 or greater

10) (1.0 or greater for subjects with EDSS at screening of 5.5) sustained at least 4 weeks plus either (i) At least 3 gadolinium-enhancing lesions (brain or spinal cord) on MRI obtained > 3 months but < 18 months after onset of the clinical relapse, and not at the site corresponding to the relapse.OR (ii) At least 3 new T2 lesions (brain or spinal cord) on MRI obtained any time up to 18 months after the relapse compared with a reference scan done > 30 days after the relapse. The magnet strength and technique must be similar in both scans.

11) On IFN or GA at least 6 months before the first relapse occurs that is counted to satisfy inclusion criterion #7 OR having received adequate doses of natalizumab or cytotoxic therapy on a treatment schedule before the first relapse occurs that is counted to satisfy inclusion criterion #7.

12) On IFN, GA, natalizumab or cytotoxic therapy when the second relapse occurs or the MRI is obtained which satisfies inclusion criterion #7.

13) Approval by an MS Review Panel that: a) verifies the adequacy of IFN/GA/natalizumab/cytotoxic, b) determines the date that the subject met the neurological eligibility criteria for the protocol, c) determines whether any progression or resolution of disability in the interval between eligibility and initiation of protocol therapy affects the appropriateness of enrollment, and d) determines if there is adequate justification to delay initiation of protocol therapy after MSRP approval.

14) The requirement to meet Karnofsky performance status >/= 70% is deleted.

15) Good clinical condition, adequate organ function & no co-existing medical problems that would significantly increase risk of the transplant procedure. Defined as: a. DLCO >/= 45% (corrected for hemoglobin), b. LVEF by MUGA or echocardiogram >/= 45%, c. Serum creatinine < 2.0 mg/dL or measured creatinine clearance > 50 mls/min, d. Bilirubin < 2.0 mg/dL unless isolated hyperbilirubinemia attributed to Gilbert's syndrome, and e. AST and ALT <= 3 x the upper limit of normal. f. Peripheral blood counts must include a platelet count >100,000/microliter and absolute neutrophil count >1500/microliter.

16) Understood and signed written informed consent, obtained prior to the study subject undergoing any study-related procedure, including screening tests.

Exclusion Criteria:1) Primary progressive MS.

2) Secondary progressive MS without relapses for >= 12 months (i.e., progression without exacerbations or relapses).

3) Neuromyelitis optica.

4) Initiation of new immunosuppressant treatment (except corticosteroids) after the subject becomes protocol-eligible: a. While awaiting initiation of protocol therapy, active disease shall be managed with corticosteroids; b. If a subject demonstrates failure to manage active disease using corticosteroids, mycophenolate mofetil or cytotoxic therapy may be used.

5) Lapse of greater than 6 months between the time a subject becomes protocol eligible and submission of the subject's information to the MSRP.

6) Prior treatment with investigational immunosuppressive drugs or agents within 3 months of protocol eligibility or after becoming protocol-eligible.

7) Positive baseline plasma and CSF PCR studies for JC virus or a brain MRI that has changes consistent with a diagnosis of PML.

8) Subjects with any history of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).

9) Active hepatitis B or hepatitis C infection or evidence of cirrhosis.

10) HIV positive.

11) Uncontrolled diabetes mellitus, defined as HbA1c > 8% and / or requiring intensive management.

12) Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic bacteriuria).

13) Any illness that in the opinion of the investigators would jeopardize the ability of the subject to tolerate aggressive chemotherapy.

14) Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the subject is judged to be cured by the administered therapy, such as head and neck cancer, or breast cancer will be considered on an individual basis.

15) Positive pregnancy test or inability or unwillingness to use effective means of birth control. Effective birth control is defined as: a. Refraining from all acts of vaginal intercourse (abstinence), b. Consistent use of birth control pills, c. Injectable birth control methods (Depo-Provera, Norplant), d. Tubal sterilization or male partner who has undergone vasectomy, e. Placement of an IUD (intrauterine device), and f. Use, with every act of intercourse, of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam.

16) Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.

17) Known hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins, or to iron compounds/medications.

18) Presence of metallic objects implanted in the body that would preclude the ability of the subject to safely have MRI exams.

19) Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance with treatment or informed consent impossible.

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Links
Registration Number: NCT00288626
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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