Scleroderma Treatment With Autologous Transplant (STAT) Study

Description

This phase II trial studies how well giving cyclophosphamide and anti-thymocyte globulin together followed by peripheral blood stem cell transplant (PBSCT) works in treating patients with systemic scleroderma. Stem cells are collected from the patient's blood and stored prior to treatament. To store the stem cells patients are given colony-stimulating factors, such as filgrastim (G-CSF) or chemotherapy (cyclophosphamide) to help stem cells move from the bone marrow to the blood so they can be collected and stored. After storage, patients are then given high-dose chemotherapy, cyclophosphamide, and immunosuppression with anti-thymocyte globulin to suppress the immune system to prepare for the transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and immunosuppression.

Study Start Date

September 2011

Estimated Completion Date

September 2019

Interventions

  • Procedure: autologous hematopoietic stem cell transplantation
  • Other: quality-of-life assessment
  • Other: Laboratory Biomarker Analysis
  • Other: questionnaire administration
  • Procedure: quality-of-life assessment
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
  • Other: laboratory biomarker analysis
  • Drug: mycophenolate mofetil
  • Biological: Anti-Thymocyte Globulin
  • Procedure: Peripheral Blood Stem Cell Transplantation
  • Drug: Plerixafor
  • Procedure: peripheral blood stem cell transplantation
  • Biological: anti-thymocyte globulin
  • Drug: plerixafor
  • Other: Questionnaire Administration
  • Biological: Filgrastim
  • Drug: Cyclophosphamide
  • Drug: cyclophosphamide
  • Biological: filgrastim
  • Drug: Mycophenolate Mofetil
  • Other: Quality-of-Life Assessment

Specialties

  • Rheumatology: Autoimmune/Heritable,Connective Tissue Dz
  • Dermatology: Autoimmune/Bullous Dz

MeSH Terms

  • Scleroderma
  • filgrastim
  • mycophenolate mofetil

Study ID

Fred Hutchinson Cancer Research Center -- 2533.00

Status

Unknown

Trial ID

NCT01413100

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

30

Sponsor

Fred Hutchinson Cancer Research Center

Inclusion Criteria

  • GROUP 1: Patients must have 1) both a and b below
  • and 2) at least one of c, d or e
  • a) Diffuse cutaneous scleroderma as defined by skin thickening proximal to the elbows and knees and/or involving the torso in addition to distal extremity involvement
  • a skin score will be obtained but not used to determine eligibility
  • b) Duration of systemic sclerosis =< 7 years from the onset of first non-Raynaud's symptom
  • for those patients with disease activity between 5-7 years from the onset of first non-Raynaud's symptom, recent progression or activity of disease must be documented for evaluation by the evaluation resource center (ERC)
  • c) Presence of SSc-related pulmonary disease with forced vital capacity (FVC) < 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide (DLCO)1 < 70% of predicted AND evidence of alveolitis by high-resolution chest computed tomography (CT) scan and/or by bronchoalveolar lavage (BAL) (if high resolution computed tomography [HRCT] fails to show ground glass, then BAL for diagnosis of alveolitis must be confirmed)
  • alveolitis by BAL cell count will be defined based on a BAL cell differential count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe
  • d) History of SSc-related renal disease that may not be active at the time of screening
  • stable serum creatinine must be documented for a minimum of 3 months post-renal crisis at the time of the baseline visit history of scleroderma hypertensive renal crisis is included in this criterion and is defined as follows:
  • e) History of new-onset hypertension based on any of the following (measurements must be repeated and confirmed at least 2 hours apart within 3 days of first event-associated observation, with a change from baseline):
  • Systolic blood pressure (SBP) >=140 mmHg
  • Diastolic blood pressure (DBP) >= 90 mmHg
  • Rise in SBP >= 30 mmHg compared to baseline
  • Rise in DBP >= 20 mmHg compared to baseline
  • AND one of the following 5 laboratory criteria:
  • Increase of >= 50 % above baseline in serum creatinine
  • Proteinuria: >= 2+ by dipstick confirmed by protein:creatinine ratio > 2.5
  • Hematuria: >= 2+ by dipstick or > 10 red blood cell (RBC)s/hematopoietic-promoting factor (HPF) (without menstruation)
  • Thrombocytopenia: < 100,000 plts/mm3
  • Hemolysis: by blood smear or increased reticulocyte count
  • The above definition of SSc hypertensive renal crisis is independent of whether concomitant anti-hypertensive medications are used
  • Subjects who present with solely skin and renal disease in the absence of other organ involvement, except classic SSc renal crisis as described above and including non-hypertensive renal crisis, must see a nephrologist to confirm that their renal disease is secondary to only SSc
  • Note: Subjects may be re-screened if they fail to meet inclusion criteria on initial evaluation
  • GROUP 2:
  • Progressive pulmonary disease as defined by a decrease in the FVC or DLCO-adjusted by 10 or 15 percent or greater, respectively, from a prior FVC or DLCO-adjusted in the previous 18-month period
  • Patients will have diffuse cutaneous disease and may have both FVC and DLCOcorr >= 70% at screening for the study
  • Patients must also have evidence of alveolitis as defined by abnormal chest CT or BAL
  • GROUP 3:
  • Diffuse scleroderma with disease duration =< 2 years since development of first sign of skin thickening plus modified Rodnan skin score >= 25 plus either
  • Erythrocyte sedimentation rate (ESR) > 25 mm/1st hour and/or hemoglobin (Hb) < 11 g/dL, not explained by causes other than active scleroderma
  • Lung involvement (either FVC or DLCO < 80% and evidence of interstitial lung disease by CT scan or alveolitis by BAL)
  • Patients in group 3 must have a left ventricular ejection fraction of > 50% by Doppler echocardiography or multi gated acquisition scan (MUGA) scan
  • If arrhythmias are evident clinically, then an evaluation by a cardiologist is required
  • GROUP 4:
  • Diffuse scleroderma with disease duration =< 2 years and skin score >= 30
  • Patients in group 4 must have a left ventricular ejection fraction of > 50% by Doppler echocardiography or MUGA scan
  • If arrhythmias are evident clinically, then an evaluation by a cardiologist is required
  • GROUP 5:
  • Limited cutaneous scleroderma and SSc-related pulmonary disease with FVC < 80% or hemoglobin-adjusted DLCO < 70% of predicted
  • AND evidence of alveolitis by high-resolution chest CT scan and/or by BAL (if HRCT fails to show ground glass, then BAL for diagnosis of alveolitis must be confirmed)
  • Alveolitis by BAL cell count will be defined based on a BAL cell differential count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe

Exclusion Criteria

  • Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival
  • this includes, but is not restricted to, subjects with any of the following:
  • Pulmonary dysfunction defined as:
  • Severe pulmonary dysfunction with (1) a hemoglobin corrected DLCO < 45% of predicted at the Clinical Review, (2) a hemoglobin-correct DLCO < 40% of predicted at the Baseline Screening visit, or (3) FVC < 45% of predicted at the Clinical review or Baseline Screening visit, or
  • pO2 < 70 mmHg or pCO2 >= 45 mmHg without supplemental oxygen, or
  • O2 saturation < 92% at rest without supplemental oxygen as measured by forehead pulse oximeter
  • Significant pulmonary artery hypertension (PAH) defined as:
  • Peak systolic pulmonary artery pressure > 50 mmHg by resting echocardiogram will require right heart catheterization
  • if pulmonary artery pressure (PAP) is not evaluable on echocardiogram due to lack of a Tricuspid regurgitant jet, then normal anatomy and function as evidenced by normal right atrium and ventricle size, shape and wall thickness and septum shape must be documented to rule-out PAH otherwise, right heart cathertization is indicated prior history of PAH but controlled with medications will not exclude patients from the protocol
  • Mean pulmonary artery pressure by right heart catheterization exceeding 30 mmHg at rest
  • if mean PAP is elevated and pulmonary vascular resistance and transpulmonary gradient are normal then the patient is eligible for the protocol
  • New York Heart Association (NYHA)/World Health Organization Class III or IV
  • Cardiac: Uncontrolled clinically significant arrhythmias
  • clinical evidence of significant congestive heart failure (CHF) (NYHA Class III or IV) left ventricular ejection fraction (LVEF) < 50% by echocardiogram or prior insertion of a pacemaker or cardioverter-defibrillator
  • History/presence of arrhythmia (even controlled) on chemical anti-arrhythmic(s) must have cardiac consult prior to randomization to ensure the subject could safely proceed with protocol requirements
  • Significant renal pathology defined as:
  • Estimated creatinine clearance (CrCl) < 40 mL/min (using Cockcroft-Gault formula based on actual body weight ) and serum creatinine > 2.0 mg/dL
  • OR
  • Active, untreated SSc renal crisis at the time of enrollment
  • Hepatic: Active hepatitis (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or bilirubin > 2 times the upper limit of normal [ULN]) or evidence of moderate to severe periportal fibrosis by liver biopsy
  • Active or clinically significant Gastric Antral Vascular Ectasia (GAVE, "watermelon stomach")
  • Unwilling or unable to discontinue disallowed disease-modifying antirheumatic drugs (DMARDs) for treatment of SSc at time of randomization
  • History or presence of a 2nd autoimmune disease requiring immunosuppressive therapy that has substantial risk of immunosuppressive treatment beyond transplant with the following exceptions:
  • History and/or presence of Sjogren's Syndrome is allowed
  • Stable myositis (A history of myositis that is clinically stable as defined by lack of progressive proximal muscle weakness and a stable or decreasing creatine phosphokinase [CPK] < 3x ULN) is allowed
  • The presence of anti-ds-deoxyribonucleic acid (DNA) without clinical systemic lupus erythematosus in a patient with a diagnosis of otherwise "pure" SSc is allowed
  • Concomitant rheumatoid arthritis without extra-articular disease characteristic of rheumatoid arthritis is allowed
  • Active uncontrolled infection that would be a contraindication to safe use of high-dose therapy
  • Positive study for Hepatitis B surface antigen or Hepatitis B or C confirmed by polymerase chain reaction (PCR)
  • Positive serology for human immunodeficiency virus (HIV)
  • Absolute neutrophil count (ANC) < 1500 cells/uL
  • Platelets < 100,000 cells/uL
  • Hematocrit < 27%
  • Hemoglobin < 9.0 g/dL
  • Malignancy within the 2 years prior to randomization, excluding adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ
  • treatment must have been completed (with the exception of hormonal therapy for breast cancer) with cure/remission status verified for at least 2 years at time of randomization
  • Presence of other comorbid illnesses with an estimated median life expectancy < 5 years
  • Evidence of myelodysplasia (MDS)
  • subjects with history of receiving any prior chemotherapy and/or radiotherapy for the treatment of malignant disease, history of greater than 2 months total prior cyclophosphamide for any condition (regardless of dose and route) and/or subjects presenting with abnormal peripheral blood counts require unilateral bone marrow aspiration for pathology, flow cytometry, cytogenetics, and fluorescence in situ hybridization (FISH) MDS panel (per institutional profile) to rule out MDS
  • Pregnancy
  • Inability to give voluntary informed consent
  • Unwilling to use contraceptive methods for at least 15 months after starting treatment

Gender

Both

Ages

69 Years and younger

Accepts Healthy Volunteers

No

Study Locations and Contact Information (20)

Study Location Distance Name Phone Email
Boston Medical Center - Boston, Massachusetts 3.5 miles None None None
Boston Medical Center - Boston, Massachusetts 3.5 miles Vaishali Sanchorawala 617-414-2507 vaishali.sanchorawala@bmc.org
Boston University School of Medicine - Boston, Massachusetts 3.5 miles None None None
Hospital for Special Surgery - New York, New York 184.8 miles None None None
Weill Medical College of Cornell University - New York, New York 187.1 miles None None None
Duke University Medical Center - Durham, North Carolina 609.0 miles None None None
University of Michigan Comprehensive Cancer Center - Ann Arbor, Michigan 645.2 miles Dinesh Khanna 734-763-3110 khannad@med.umich.edu
University of Michigan Comprehensive Cancer Center - Ann Arbor, Michigan 645.2 miles None None None
The University of Texas Health Science Center Houston - Houston, Texas 1,609.9 miles Maureen Mayes 713-500-6905 Maureen.D.Mayes@uth.tmc.edu
The University of Texas Health Science Center Houston - Houston, Texas 1,609.9 miles None None None
M D Anderson Cancer Center - Houston, Texas 1,609.9 miles None None None
M D Anderson Cancer Center - Houston, Texas 1,609.9 miles Chitra Hosing 713-794-5745 cmhosing@mdanderson.org
Colorado Blood Cancer Institute - Denver, Colorado 1,766.9 miles None None None
Seattle Childrens Hospital - Seattle, Washington 2,487.2 miles Anne Stevens 206-987-2057 anne.stevens@seattlechildrens.org
Seattle Childrens Hospital - Seattle, Washington 2,487.2 miles None None None
Fred HutchUniversity of Washington Cancer Consortium - Seattle, Washington 2,490.2 miles None None None
City of Hope Comprehensive Cancer Center - Duarte, California 2,578.2 miles Stephen J Forman 626-359-8111 sforman@coh.org
City of Hope Comprehensive Cancer Center - Duarte, California 2,578.2 miles None None None
UCLA Jonsson Comprehensive Cancer Center - Los Angeles, California 2,605.2 miles None None None
UCLA Jonsson Comprehensive Cancer Center - Los Angeles, California 2,605.2 miles Daniel Furst 310-206-5366 defurst@mednet.ucla.edu

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