Reduced Intensity Transplant in Medically Refractory Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc) - Full Text View

Sponsored by:	Columbia University
Information provided by:	Columbia University
ClinicalTrials.gov Identifier:	NCT00684255

Purpose

The purpose of this study is to determine if a reduced intensity (RI) (non-myeloablative) chemoimmunotherapy followed by AlloSCT (matched family donors and matched unrelated cord blood donors) will be well tolerated and result in a high degree of mixed or complete donor chimerism and stabilization of autoimmune disease in a select group of patients with medically refractory SLE or SSc.

Primary Outcomes: To determine the toxicity associated with a reduced intensity regimen consisting of fludarabine/busulfan and alemtuzumab (FBA) followed by AlloSCT in selected patients with medically refractory SLE or SSc; to quantitate the percent of mixed and/or complete donor chimerism, measure immune reconstitution, determine probability of progression free and overall survival and determine the incidence of pre-existing maternal-fetal derived microchimerism (<1%) and the changes in microchimerism following a RI regimen of FBA and AlloSCT in selected patients with medically refractory SLE or SSc. Secondary Outcomes: To determine the feasibility, toxicity, and response of donor lymphocyte infusion (if available) (adoptive cellular immunotherapy) in selected patients with medically refractory SLE or SSc after day +180 with <50% mixed donor chimerism and progressive disease following FBA RI conditioning and AlloSCT; to measure the changes in humoral and cellular autoimmune biomarkers before and after mixed donor chimerism, and to estimate the probability and severity of acute and chronic graft versus host disease (GVHD) following FK-506/mycophenolate mofetil (MMF) prophylaxis following FBA RI conditioning and AlloSCT in selected patients with medically refractory SLE or SSc; and to determine the quality of life before and after FBA RI conditioning and AlloSCT in selected patients with medically refractory SLE or SSc.

Condition	Intervention	Phase
Systemic Lupus Erythematosus Systemic Sclerosis	Drug: Reduced Intensity Allogeneic Transplant	Phase I

MedlinePlus related topics: Autoimmune Diseases Lupus Scleroderma

Drug Information available for: Campath Alemtuzumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Reduced Intensity Conditioning And Allogeneic Stem Cell Transplantation in Patients With Medically Refractory Systemic Lupus Erythematosus and Medically Refractory Systemic Sclerosis (SSc)

Further study details as provided by Columbia University:

Primary Outcome Measures:

To determine the toxicity associated with reduced intensity regmien of fludarabine/busulfan and Campath followed by allogeneic stem cell transplant in patients with medically refractory SLE or SSc [ Time Frame: until end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To quantitate the percent of mixed and/or complete donor chimerism. [ Time Frame: until end of study ] [ Designated as safety issue: No ]
To measure immune reconstitution. [ Time Frame: until end of study ] [ Designated as safety issue: No ]
To determine the probability of progression free and overall survival. [ Time Frame: Until end of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	August 2007
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Fludarabine 30 mg/m2 Day -7, -6, -5, -4, -3, -2 Busulfan 3.2 mg/kg Days _8, -7, -6, -5 Alemtuzumab 2 mg/m2 Day -5 Alemtuzumab 6 mg/m2 Day -4, -3 Alemtuzumab 20 mg/m2 Day -2

Eligibility

Ages Eligible for Study:	7 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diffuse Systemic Sclerosis and variants as per ACR criteria
Medically refractory disease (All of the following):
- Failure of two or more drugs/drug combinations of at least steroids and either cyclophosphamide or methotrexate
- Failure defined as disease persistence/progression and/or intolerable drug side effects (i.e. AVN, osteoporosis (z score <1.5), grade 3/4 hypertension, grade 3/4 infections)
History of at least one of the following:
- Cardiac (one of the following)
  - LVEF >40% but 55% and/or
  - SF >20% but 28%
- Pulmonary
  - Uncorrected DLCO 40% but <70% and/or
  - Pulmonary fibrosis on CXR or CT
- Musculoskeletal
  - Disabling flexion contractures and/or ulcerations
- Gastrointestinal
  - Progressive oral/esophageal or colonic dysmotility
- Renal
  - Grade II proteinuria, hematuria and/or nephritis
- Rodnan Score 15
Organ Function as defined below:
- Pulmonary function defined as:
  - DLCO >40% by pulmonary function test OR For children who are uncooperative a pulse oximetry >94%
- Renal function defined as (Any one):
  - Serum creatinine 1.5 x normal, and/or 24 hour creatinine clearance >40 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- Cardiac function defined as:
  - Shortening fraction of >20% by echocardiogram (see Appendix VII)
- Liver function defined as:
  - SGOT (AST) or SGPT (ALT) <5 x upper limit of normal
Karnofsky/Lansky >60%

Diagnosis of SLE by ACR criteria

Medically refractory disease (All of the following):
- Failure of 3 drugs/drug combinations including at least steroids and cyclophosphamide
- Failure defined as disease persistence/progression and/or intolerable drug side effects (i.e. AVN, osteoporosis (z score <1.5), grade 3/4 hypertension, grade 3/4 infections)
History of at least one high risk feature
- Grade III/IV nephritis
- Grade III/IV hypertension
- Grade IV cytopenia
- Grade II-IV neuropsychiatric lupus
- Musculoskeletal with 3 joints affected
- Heart failure (AHA Class II)
- Pulmonary disease DLCO 40% and 70%
Organ Function as defined below:
- Pulmonary function defined as:
  - Uncorrected DLCO >40% by pulmonary function test OR For children who are uncooperative a pulse oximetry >94%
- Renal function defined as (Any one):
  - Serum creatinine 1.5 x normal, and/or 24 hour creatinine clearance >40 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- Cardiac function defined as:
  - Shortening fraction of >20% by echocardiogram (see Appendix VII)
- Liver function defined as:
  - SGOT (AST) or SGPT (ALT) <5 x upper limit of normal
Karnofsky/Lansky >60%

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00684255

Contacts

Contact: MItchell S Cairo, MD	212-305-8316	mc1310@columbia.edu
Contact: Ginny Kohl, RN	212-305-7213	vk2172@columbia.edu

Locations

United States, New York
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Mitchell Cairo, MD 212-305-8316 mc1310@columbia.edu
Contact: Ginny Kohl, RN 212-305-7213 vk2172@columbia.edu
Sub-Investigator: Prakash Satwani, MD
Sub-Investigator: Monica Bhatia, MD
Sub-Investigator: Diane George, MD

Sponsors and Collaborators

Columbia University

Investigators

Principal Investigator:

Mitchell Cairo, MD

Columbia University

More Information

No publications provided

Responsible Party:	Columbia University ( Mitchell S. Cairo, MD/ Principal Investigator )
Study ID Numbers:	CHNY-01-511, AAAB1324
Study First Received:	May 22, 2008
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00684255 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Columbia University:

Autoimmune Disease
Reduced Intenstiy Transplant

Study placed in the following topic categories:

Autoimmune Diseases
Skin Diseases
Lupus
Sclerosis
Fludarabine monophosphate
Lupus Erythematosus, Systemic
Alemtuzumab

Busulfan
Connective Tissue Diseases
Scleroderma, Diffuse
Scleroderma
Scleroderma, Systemic
Fludarabine

Additional relevant MeSH terms:

Pathologic Processes
Autoimmune Diseases
Skin Diseases
Immune System Diseases
Lupus Erythematosus, Systemic

Connective Tissue Diseases
Scleroderma, Diffuse
Sclerosis
Scleroderma, Systemic

ClinicalTrials.gov processed this record on May 07, 2009