Clinical trial NCT00014755: Phase I Pilot Study of Total-Body Irradiation, Anti-Thymocyte Globulin and Cyclophosphamide Followed By Syngeneic or Autologous Peripheral Blood Stem Cell Transplantation in Patients With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: multiple sclerosis
neurologic and psychiatric disorders
rare disease
Lead sponsor: Office of Rare Diseases (ORD)
Sponsor class: NIH
First posted: 2001-04-11
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: OBJECTIVES: I. Determine the toxicity of total-body irradiation, anti-thymocyte globulin, and cyclophosphamide followed by syngeneic or autologous peripheral blood stem cell (PBSC) transplantation in patients with multiple sclerosis.

II. Determine the disease response of patients treated with this regimen. III. Determine the safety and efficacy of filgrastim (G-CSF) for PBSC mobilization in this patient population.

Detailed description: PROTOCOL OUTLINE: This is a multicenter study. Patients receive oral prednisone on days 0-10. Beginning on day 1, patients undergoing autologous peripheral blood stem cell (PBSC) transplantation receive filgrastim (G-CSF) subcutaneously daily until leukapheresis is completed. Leukapheresis begins on approximately day 4 and continues until adequate CD34+ PBSC are collected.

PBSC are collected from syngeneic donors in a similar manner. Patients undergo total-body irradiation twice daily on days -5 and -4. Patients receive cyclophosphamide IV on days -3 and -2 and anti-thymocyte globulin IV on days -5, -3, -1, 1, 3, and 5. Patients undergo autologous or syngeneic PBSC transplantation on day 0. Following PBSC transplantation, patients receive oral prednisone on days 7-30 and G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

Patients are followed at 30, 80, and 90 days, monthly for 6 months, and then at 1 and 2 years.

Eligibility criteria: PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of rapidly progressive multiple sclerosis (MS) by Proser criteria and at high risk for a fatal outcome or severe disability with one of the following:

* Primary progressive disease
* Relapsing/remitting disease with 2 or more attacks in 2 years
* Secondary progressive disease

Extended disability status scale (EDSS) between 5.0 and 8.0 with deterioration in the EDSS of 1 or more points over the past year

More than 60 days since relapse of MS

No evidence of myelodysplasia

Sibling donor proven to be an identical twin by ABO typing, HLA typing, and VNTR analysis (for syngeneic transplantation)

--Prior/Concurrent Therapy--

Radiotherapy: No prior total-lymphoid irradiation

Other: No other concurrent investigational agents

--Patient Characteristics-- Hepatic: No hepatic impairment that would preclude high-dose immunosuppressive therapy

Renal: No renal impairment that would preclude high-dose immunosuppressive therapy

Cardiovascular: No cardiac impairment that would preclude high-dose immunosuppressive therapy

Pulmonary: No pulmonary impairment that would preclude high-dose immunosuppressive therapy

Other:

* No neurologic impairment that would preclude high-dose immunosuppressive therapy
* No active uncontrolled infection
* No active malignancy
* No other illness that would severely limit life expectancy
* No medical or psychiatric conditions that would preclude study
* No history of hypersensitivity to murine proteins or E. coli-derived proteins
* No demonstrated lack of compliance with prior medical care
* Able to undergo an MRI scan
* HIV negative
* Not pregnant or nursing

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Saint Louis
country: United States
facility: Washington University Barnard Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Richard Nash
role: STUDY_CHAIR
References:
citation: Bowen JD, Kraft GH, Wundes A, Guan Q, Maravilla KR, Gooley TA, McSweeney PA, Pavletic SZ, Openshaw H, Storb R, Wener M, McLaughlin BA, Henstorf GR, Nash RA. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant. 2012 Jul;47(7):946-51. doi: 10.1038/bmt.2011.208. Epub 2011 Nov 7.