Scleroderma: Cyclophosphamide or Transplantation (SCOT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00114530
First received: June 15, 2005
Last updated: February 22, 2013
Last verified: February 2013

June 15, 2005
February 22, 2013
June 2005
June 2016   (final data collection date for primary outcome measure)
Global rank composite score (GRCS) at 54 months post- randomization. [ Time Frame: At 54 Months Post-Randomization ] [ Designated as safety issue: Yes ]
The GRCS reflects each participant's "order" relative to every other participant based on the following hierarchy of component outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Modified Scleroderma Health Questionnaire (SHAQ), and modified Rodnan Skin Score (mRSS).The analysis for the global rank composite score is based on an extension of the Wilcoxon signed-rank test.
Survival without significant organ damage
Complete list of historical versions of study NCT00114530 on ClinicalTrials.gov Archive Site
  • Treatment-related mortality [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
    defined as death occurring at any time after randomization and definitely or probably resulting from treatment given in the study.
  • Mortality due to any cause [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Regimen-related toxicities defined as adverse events (AEs) Grade 3 or worse [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Infectious complications [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Engraftment (for the High-dose immunosuppressive therapy followed by stem cell transplantation arm only) [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • A decrease of more than in 0.4 on two successive Modified Scleroderma Health Assessment Questionnaires (SHAQ)taken within 3 months of each other [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • Quality of life as measured by the Short Form 36 (SF-36) [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • Pulmonary function measured by Diffusion in Liters of Carbon Monoxide (DLCO) [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Pulmonary function measured by Forced Vital Capacity (FVC) [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Skin condition as indicated by Modified Rodnan Skin Score (mRSS) [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • New or worsening arrhythmias, congestive heart failure (CHF), or pericardial effusion [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
    New or worsening arrhythmias that require medical treatment of 3 months or more or require ablative therapy or pacemaker insertion OR congestive heart failure (CHF) requiring clinical treatment for 3 months or more OR pericardial effusion occurs that requires pericardial window
  • New or worsening pulmonary hypertension [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Occurrence of scleroderma renal crisis [ Time Frame: Month 72 ] [ Designated as safety issue: Yes ]
  • Documented myositis, requiring more than 30 mg per day of prednisone for over 1 month [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • Increase in Modified Scleroderma Health Assessment Questionnaire (SHAQ) by more than 0.4 from baseline on 2 successive occasions within 3 months [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • Decrease in quality of life as measured by the Short Form 36 (SF-36) [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • Initiating use of disease-modifying antirheumatic drugs [ Time Frame: Month 72 ] [ Designated as safety issue: No ]
  • Global rank composite score (GRCS) at 48 months post-randomization. [ Time Frame: At 48 Months Post-Randomization ] [ Designated as safety issue: Yes ]
  • Event-free Survival (EFS) at 48 and 54 months after randomization. [ Time Frame: At 48 and 54 Months Post-Randomization ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Scleroderma: Cyclophosphamide or Transplantation (SCOT)
A Randomized, Open-Label, Phase II Multicenter Study of High-Dose Immunosuppressive Therapy Using Total Body Irradiation, Cyclophosphamide, ATGAM, and Autologous Transplantation With Auto-CD34+HPC Versus Intravenous Pulse Cyclophosphamide for the Treatment of Severe Systemic Sclerosis (SCSSc-01)

Severe systemic sclerosis (SSc) is a serious autoimmune disorder in which a person's own immune cells attack organs in the body. SSc affects the skin, joints, lungs, heart, intestinal tract, and kidneys, and half of the patients with the most severe organ involvement die within 5 years. Treatment for SSc usually includes supportive care or immunosuppressive drugs (drugs to suppress the immune system). As the immune cells are believed to be causing the disease, researchers are looking for new therapies that either slow down or stop this process, while not being too toxic.

The main purpose of this study is to determine the safety and effectiveness of high-dose immunosuppressive therapy followed by reinfusion (transplantation) of the participant's own autologous (self) peripheral blood stem cells (PBSCs) compared to treatment with monthly (for 12 months) intravenous doses of cyclophosphamide (Cytoxan) therapy for the treatment of severe systemic sclerosis (SSc). These treatments are being given in order to determine if they will slow down or stop SSc from becoming more severe, and if they can reverse the effects of the disease. The researchers are evaluating the effects of the two treatments on serious organ damage and survival related to SSc, while also looking at the side effects of the two treatments.

This trial also includes three optional mechanistic sub-studies open to a subset of participants enrolled in the SCOT trial:

  1. Pharmokinetics of 4-hydroxycyclophosphamide in Patients Receiving Cyclophosphamide for the SCOT trial (Originally listed separately as DAIT SCSSc-01-01, NCT00848614). The purpose of this study is to determine the plasma concentration and exposure time required for cyclophosphamide to produce optimal immunosuppressive activity with minimal toxicity in participants with severe systemic sclerosis.
  2. Vascular Progenitor Cells and the Pathogenesis of Systemic Sclerosis(Originally listed separately as DAIT SCSSc-01-02, NCT00871221). The purpose of this study is to measure and characterize the circulating endothelial progenitor cells from the blood of 30 participants and also to determine the extent of vascular cell apoptosis and proliferation in cutaneous microvasculature in these participants before and after the receipt of the two SCOT treatment regimens.
  3. Molecular Analysis of T Cell Immune Recovery for the SCOT Trial(Originally listed separately as DAIT SCSSc-01-03, NCT00872508). The purpose of this study is [1] to describe the condition of peripheral T cell reactivity and repertoire diversity in SSc patients and evaluate evidence for potential defects prior to randomization, [2] to gain a better understanding of the impact of cyclophosphamide (Cytoxan) and high-dose immunosuppressive therapy with autologous stem cell transplantation on thymopoiesis, and [3] to describe the kinetics and breadth of T cell immune recovery in SSc patients treated with these interventions.
Not Provided
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Scleroderma, Systemic
  • Sclerosis
  • Autoimmune Disease
  • Procedure: Autologous stem cell transplantation
    transplantation of blood stem cells from participant's bone marrow or blood
  • Drug: Cyclophosphamide
    Other Name: Cytoxan
  • Drug: Antithymocyte globulin, equine
  • Drug: Methylprednisolone
  • Drug: Growth colony stimulating factor (G-CSF)
  • Radiation: Total body irradiation (TBI)
    used to eradicate the immune system thought to be causing the systemic sclerosis
  • Experimental: High-dose immunosuppressive therapy followed by HSCT
    Participants will first have hematopoietic stem cells removed from their blood. They then will receive high doses of chemotherapy and radiation to eliminate their developed and presumably abnormal immune system, followed by autologous stem cell transplantation to reintroduce the purified stem cells to re-establish their immune system.
    Interventions:
    • Procedure: Autologous stem cell transplantation
    • Drug: Cyclophosphamide
    • Drug: Antithymocyte globulin, equine
    • Drug: Methylprednisolone
    • Drug: Growth colony stimulating factor (G-CSF)
    • Radiation: Total body irradiation (TBI)
  • Experimental: High-dose pulse IV cyclophosphamide (Cytoxan)
    Participants will receive high doses of intravenous cyclophosphamide. The dose being used in this study is about 50% higher than that commonly used by most physicians to treat many other autoimmune diseases. 12 monthly pulses of IV CTX (initial dose of 500 mg/m2, followed by 11 doses of 750 mg/m2) are administered.
    Intervention: Drug: Cyclophosphamide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
114
June 2016
June 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Severe systemic sclerosis (SSc) as defined by the American College of Rheumatology (ACR)
  • SSc, including extensive skin and internal organ involvement involving either the lungs or the kidneys, that threatens participant's life
  • Willingness to use accepted methods of contraception for at least 15 months after starting study treatment

Exclusion Criteria:

  • Lung, heart, liver, or kidney impairment that would interfere with the study or compromise participant's survival
  • Active blood vessel dilation in the stomach (Active Gastric Antral Vascular Ectasia/GAVE, also known as "watermelon stomach"). Patients found to have this disorder at study screening can receive treatment outside the study and then be re-screened. For more information about this study criterion, refer to the study protocol.
  • Previous treatment with cyclophosphamide, as defined by: a) prior IV cyclophosphamide administration for more than 6 months OR a total cumulative IV dose greater than 3 g/m2; b) prior oral cyclophosphamide administration for more than 4 months, regardless of dose; or c) combination of prior oral and IV cyclophosphamide administration for more than 6 months, independent of dose.
  • Steroid therapy at doses of greater than 10 mg/day, or more than 2 pulses for concurrent illnesses within prior 12 months
  • Unwillingness or inability to discontinue certain disease-modifying antirheumatic drugs (DMARDs) for the treatment of SSc
  • Presence of clinically significant rheumatic diseases other than scleroderma requiring significant immunosuppression
  • Any active uncontrolled infection that would interfere with high-dose therapy or pulse cyclophosphamide regimens
  • Hepatitis B virus infected
  • Hepatitis C virus infected
  • HIV infected
  • Blood abnormalities
  • Diagnosis of cancer within 2 years prior to study entry. Participants with adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ are not excluded.
  • Other comorbid illnesses with an estimated life expectancy of less than 5 years
  • Defective formation of bone marrow cells (myelodysplasia)
  • Uncontrolled hypertension
  • History of hypersensitivity to murine or E. coli proteins
  • History of noncompliance with prior medical care
  • History of substance abuse within 5 years prior to study entry
  • Pregnancy
Both
18 Years to 69 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00114530
DAIT SCSSc-01, SCOT
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Keith Sullivan, MD Division of Cellular Therapy, Duke University
Study Chair: Daniel Furst, MD Rheumatology Division, UCLA Medical School
Study Chair: Peter McSweeney, MD Blood and Marrow Transplant Program, Presbyterian/St. Luke's Medical Center, Rocky Mountain Cancer Center
Principal Investigator: Leslie Crofford, MD University of Kentucky
Principal Investigator: Maureen Mayes, MD, MPH The University of Texas Health Science Center, Houston
Principal Investigator: Richard Nash, MD Fred Hutchinson Cancer Research Center
National Institute of Allergy and Infectious Diseases (NIAID)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP