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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 19 February 2015
Main ID:  NCT01047072
Date of registration: 11/01/2010
Prospective Registration: Yes
Primary sponsor: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Public title: Low-Dose Conditioning Followed by Donor Stem Cell Transplant in Treating Patients With Severe Systemic Sclerosis
Scientific title: Phase II Clinical Trial of Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Patients With Severe Systemic Sclerosis
Date of first enrolment: January 2010
Target sample size: 0
Recruitment status: Withdrawn
URL:  http://clinicaltrials.gov/show/NCT01047072
Study type:  Interventional
Study design:  Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment  
Phase:  Phase 2
Countries of recruitment
United States
Contacts
Name:     George Georges
Address: 
Telephone:
Email:
Affiliation:  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients with severe SSc as defined by the American College of Rheumatology and at
high-risk for a fatal outcome based on the following prognostic factors from
groups 1-5:

- Group 1: Patients with 1) both a. and b. below; and 2) at least one of c., d. or
e:

- a. Diffuse cutaneous scleroderma with skin score of >= 16 (modified Rodnan
skin scale)

- b. Duration of systemic sclerosis =< 5 years from the onset of first
non-Raynaud's symptom

- c. Presence of interstitial lung disease with FVC or DLCOcorr =< 70% of
predicted and evidence of alveolitis (abnormal bronchoalveolar lavage [BAL]
or high resolution chest computed tomography [CT] scan)

- d. Left heart failure with left ventricular ejection Fraction (LVEF) < 50%
or pericardial effusion (mild-moderate) or 2nd or 3rd Atrial-Ventricular
(AV) block; Myocardial disease not secondary to SSc must be excluded by a
cardiologist

- e. History of SSc-related renal disease that is not active at the time of
screening; History of scleroderma hypertensive renal crisis is included in
this criterion

- Group 2: Patients will have progressive pulmonary disease as the primary
indication for transplant as defined by a decrease in the FVC or DLCO by 15
percent or greater in the previous 12-month period. In addition, patients may
have either less skin involvement than group 1 (mRSS < 16) if they have a
history of diffuse cutaneous disease and the FVC or DLCOcorr is < 70% or both
FVC and DLCOcorr >= 70% if they have diffuse cutaneous disease (mRSS > 16) at
screening for the study; Patients must also have evidence of alveolitis as
defined by abnormal chest CT or BAL

- Group 3: Have progressive active SSc after prior autologous HCT based on the
presence of progressive pulmonary disease; This will be defined by a decrease in
the FVC since prior autologous transplant by 10 percent or greater, or DLCO
since prior autologous transplant by 15 percent or greater in addition to
evidence of alveolitis as defined by chest CT changes or BAL; If patients had
prior autologous HCT on the SCOT clinical trial, they must have failed based on
the defined study endpoints and be approved by the protocol principal
investigator (PI)

- Group 4: Patients who meet group 1 inclusion criteria but have FVC or DLCO < 70%
plus have had an adverse event to cyclophosphamide preventing its further use
(i.e., hemorrhagic cystitis, leucopenia with WBC, 2000 or ANC < 1000 or platelet
count < 100,000 and other adverse events)

- Group 5: Diffuse scleroderma with disease duration =< 2 years since development
of first sign of skin thickening plus modified Rodnan skin score >= 25 plus ESR
> 25 mm/1st hour and/or Hb < 11 g/dL not explained by causes other than active
scleroderma.

2. Unless patients have a DLCOcorr less than 45%, patients must have failed either oral
or intravenous cyclophosphamide regimen defined as:

- IV cyclophosphamide administration for > 6 months or a total cumulative IV dose
of 6 g/m^2, or

- oral cyclophosphamide administration for > 6 months regardless of dose, or

- combination of oral and IV cyclophosphamide for > 6 months independent of dose

3. Patient must have a sibling who is a) HLA-identical and b) could serve as a donor of
a peripheral blood stem cell graft to be placed on the transplant arm or an
unrelated donor matched at HLA-A, B, C, DRB1 and DQB1. Patients without an
HLA-identical sibling or an HLA-matched unrelated donor that meet the above criteria
will be placed on the non-transplant arm

DONOR:

- The donor must be an HLA-identical sibling of the patient or an HLA-matched unrelated
donor.

- If the donor has reached the age of assent, then they must have completed the local
institutional review board (IRB) assent process.

- Donor must consent to G-CSF administration and to leukapheresis for HSC collection.

- Donor must have adequate veins for leukapheresis or agree to placement of central
venous catheter (femoral, subclavian).

- Age 12-75 years; Pediatric donors must be > 50 kg body weight.

Exclusion Criteria:

- Eligible for the NIH-sponsored randomized clinical trial (SCOT)

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months or until immunosuppression is discontinued following transplantation

- Evidence of ongoing active infection

- Pregnancy

- Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their
ability to receive therapy and compromise their survival. This includes but is not
restricted to, subjects with any of the following:

- Severe pulmonary dysfunction defined as:

1. A hemoglobin corrected DLCOcorr < 30% or FVC < 40% of predicted; or

2. O2 saturation < 92% at rest without supplemental oxygen; or

3. PO2 < 70 mmHg or pCO2 > 50 mmHg without supplemental oxygen

- Significant uncontrolled pulmonary hypertension defined as:

1. Pulmonary artery peak systolic pressure > 45 mmHg by echocardiogram and
mean pulmonary artery pressure by right heart catheterization
exceeding 32 mmHg at rest or 42 mm Hg during exercise; or

2. New York Heart Association (NYHA)/World Health Organization (WHO)
classification for pulmonary hypertension, Class III or IV

- Cardiac: Uncontrolled clinically significant arrhythmias; clinical evidence of
significant cardiac disease (NYHA Class III or IV); LVEF < 40% by echocardiogram

- Significant renal pathology, defined as:

1. Estimated CrCl < 60 mL/min (using Cockcroft-Gault formula based on actual
body weight) or serum creatinine > 2.0 mg/dL OR

2. Active, untreated SSc renal crisis at the time of enrollment

- Active hepatitis or liver biopsy evidence of cirrhosis or periportal fibrosis.
Total bilirubin > 2.5 x the upper limit of normal (and not related to Gilbert's
syndrome) and/or Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) > 4 x the upper limit of normal

- Pati



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both
Health Condition(s) or Problem(s) studied
Systemic Scleroderma
Intervention(s)
Biological: rituximab
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Drug: tacrolimus
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Primary Outcome(s)
Event-free survival [Time Frame: 2 years]
Secondary Outcome(s)
Event-free survival [Time Frame: 5 years]
Incidence of definite and probable viral, fungal, and bacterial infections [Time Frame: Up to 5 years]
Incidence of initiation of any SSC disease-modifying therapy other than that specified in the protocol treatment arms [Time Frame: Up to 5 years]
Median time to engraftment as defined as having greater than or equal to 5% donor T cells in the peripheral blood (donor T cell chimerism) [Time Frame: From date of transplant to time of engraftment]
Overall survival [Time Frame: 2 years]
Overall survival [Time Frame: 5 years]
Probability of acute and chronic GVHD [Time Frame: Up to 5 years]
Rate of primary graft failure [Time Frame: Day 56]
Rate of secondary graft failure [Time Frame: 1 year]
Time to progression [Time Frame: 2 years]
Time to progression [Time Frame: 5 years]
Secondary ID(s)
2363.00
NCI-2012-00139
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
National Cancer Institute (NCI)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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