Scleroderma Treatment With Autologous Transplant (STAT) Study

NCT01413100 | Completed Phase 2 Results DMC

• 5 other identifiers: 2533.00NCI-2011-011902533P30CA015704RG1711052
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 12

Brief Summary

This phase II trial studies how well giving cyclophosphamide and anti-thymocyte globulin together followed by peripheral blood stem cell transplant (PBSCT) and mycophenolate mofetil works in treating patients with systemic scleroderma (SSc). Stem cells are collected from the patient's blood and stored prior to treatment. 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. After the stem cells have "engrafted" and have matured enough to support the immune system at approximately 2-3 months, patients are given a medication called mycophenolate mofetil (MMF) or Myfortic. This medication is given to prevent worsening or reactivation of SSc and is referred to as maintenance therapy.

Conditions

Systemic Scleroderma

Outcome Measures

Primary Outcomes (1)

• EFS of Patients Undergoing Transplant

  Event Free Survival (EFS) was defined as survival without meeting the protocol defined endpoint of organ injury (kidney injury requiring renal replacement dialysis for \>6 months, sustained LVEF \<30%, or sustained decline of FVC \>20%).

  At 5 years

Secondary Outcomes (15)

• All-cause Mortality

  At 5 years

• The Number of Participants With Stable or Improved LVEF

  From baseline to year 5

• Number of Participants Requiring Dialysis

  From baseline to year 5

• The Number of Participants With Disease Progression

  baseline to year 5

• The Number of Participants Who Completed ALL Health Care Utilization as Assessed by UCSD Healthcare Utilization Surveys

  From baseline to 5 years

Study Arms (1)

Treatment (HDIT autologous PBSCT)

EXPERIMENTAL

STEM CELL MOBILIZATION AND PREPARATION: Patients receive filgrastim SC on mobilization days 1-4 followed by apheresis until a target dose of CD34+ cells \>= 2.5 x 10\^6/kg are collected. Patients difficult to mobilize with filgrastim alone receive cyclophosphamide IV or \*plerixafor SC on mobilization days 1-2 and filgrastim SC on mobilization days 5-7. HDIT CONDITIONING: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days -5 to -2 and anti-thymocyte globulin IV on days -5, -3, -1, 1, 3, and 5. TRANSPLANTATION: Patients undergo autologous PBSCT on day 0. MAINTENANCE THERAPY: Beginning 2-3 months after transplant, patients receive mycophenolate mofetil PO BID for 2 years.

Biological: Anti-Thymocyte Globulin; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Plerixafor; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Treatment (HDIT autologous PBSCT)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: Autologous Stem Cell Transplantation

Treatment (HDIT autologous PBSCT)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (HDIT autologous PBSCT)

Filgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim

Treatment (HDIT autologous PBSCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (HDIT autologous PBSCT)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (HDIT autologous PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (HDIT autologous PBSCT)

Plerixafor DRUG

Given SC

Also known as: AMD 3100, JM-3100, Mozobil, SDZ SID 791

Treatment (HDIT autologous PBSCT)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (HDIT autologous PBSCT)

Questionnaire Administration OTHER

Ancillary studies

Treatment (HDIT autologous PBSCT)

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with SSc as defined by the American College of Rheumatology with diffuse cutaneous disease (except Group 5) at risk of disease progression
• Patients must have failed a prior \>= 4-mponth course of either MMF/Myfortic or cyclophosphamide before being eligible for the study (determined at \>= 1 week before start of mobilization); "failure" is defined as evidence of disease progression or absence of improvement; the response prior to MMF of cyclophosphamide will be assessed by the participating site study rheumatologist
• Patients must meet eligibility in at least 1 of the following 6 groups:
• GROUP 1:
• Patients must have 1) both a and b below; and 2) either c, or d
• 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
• c) Presence of SSc-related pulmonary disease with forced vital capacity (FVC) \< 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide (DLCO) \< 70% of predicted AND evidence of alveolitis or SSc-related interstitial lung disease by high-resolution chest computed tomography (CT) scan and/or by bronchoalveolar lavage (BAL) (interstitial lung disease may be nonspecific interstitial pneumonia \[NSIP\] or usual interstitial pneumonia \[UIP\]; a bronchoalveolar lavage \[BAL\] should be done to confirm the findings of alveolitis only if the high resolution CT scan \[HRCT\] fails to show findings typically associated with systemic sclerosis changes \[ground glass NSIP, UIP, SSc related interstitial lung disease\]); 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:
• 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:

You may not qualify if:

• 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 \< 40% of predicted at the Baseline Screening visit, or (3) FVC \< 45% of predicted Baseline Screening visit, or
• Partial pressure (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 catheterization is indicated; prior history of PAH but controlled with medications will not exclude patients from the protocol; PAH is considered controlled with medications if peak systolic pulmonary artery pressure is \< 45 mmHg or mean pulmonary artery pressure by right heart catheterization is \< 30 mmHg at rest
• 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
• History/presence of arrhythmia (even controlled) on chemical anti-arrhythmic(s) must have cardiac consult 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; presence of nephrotic range proteinuria (defined as \>= 3.5 gms/24 hours, or protein:creatinine ratio \>= 3.5), active urinary sediment, urinary RBCs \> 25 per HPF, or red cell casts require further investigation by a nephrologist to rule out glomerulonephritis, overlap syndromes, or other causes of renal disease in all subjects; subjects with glomerulonephritis or overlap syndromes will be excluded
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center, Houston

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Zielonka J, Higuero Sevilla JP. Autologous hematopoietic stem cell transplant for systemic sclerosis associated interstitial lung disease. Curr Opin Rheumatol. 2024 Nov 1;36(6):410-419. doi: 10.1097/BOR.0000000000001050. Epub 2024 Sep 27.

  PMID: 39348419 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

Antilymphocyte Serum; thymoglobulin; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; plerixafor; ferric pyrophosphate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Health Care Utilization by UCSD Healthcare Utilization Survey and Work Productivity Survey: data was not collected as outlined in study. Only grade 3-5 AE assessed from start of mobilization- Day +100 post tx, excluding expected mobilization and transplant related AE's. No expected AE of grade 3-4 were captured per study. Also, AE were assessed from Day +101- day + 365 post tx (Grade 4-5). Per study, only grade 4 and 5 were captured. No grade 1-3 AE were captured per study.

Results Point of Contact

• Title: Dr. Leona Holmberg
• Organization: Fred Hutchinson Cancer Center

lholmb@fredhutch.org

206-667-6447

Study Officials

• Leona Holmberg

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 8, 2011
• First Posted: August 10, 2011
• Study Start: September 15, 2011
• Primary Completion: September 15, 2023
• Study Completion: September 11, 2024
• Last Updated: January 7, 2025
• Results First Posted: January 7, 2025

Record last verified: 2024-12

Locations

US (12)