Currently recruiting
Transplantation with T-Cell Depleted Autologous Peripheral Stem
Cells (ASCT) for Severe Systemic Sclerosis (SSc): A Phase 1 Dose
Escalation Study
Study sponsor:
The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS), and Amgen, Baxter Healthcare, Ortho Biotech, and
Sangstat corporations. All treatment costs related to the research
study are covered by a contract from NIAMS or through the General
Clinical Research Center (GCRC) at the University of Pittsburgh.
Coordinating center:
University of Pittsburgh Cancer Institute and University of
Pittsburgh Arthritis Center. CONTACTS: Thomas A. Medsger, Jr., MD at
412-383-8734, by e-mail at medsger@msx.dept-med.pitt.edu, or Carol
Blair, RN, at 412-383-8672.
Design:
This NIAMS contract is to perform ASCT in 15 diffuse cutaneous (dc)
SSc subjects with rapidly progressive skin thickening. The
differences in this protocol from those reported and used at other
centers are: (1) novel preparative regimen to maximize lymphoid
ablation while reducing non-hematologic toxicity (fludarabine plus
dose escalation of cyclophosphamide, ATG but no radiation) and (2)
more rigorous T-cell depletion of the graft to reduce the likelihood
of reintroducing the disease via contaminating autoimmune T-cells
(positive [CD34]/negative [CD2] selection using the Baxter Isolex
300i instrument). To the extent possible, given the limitations of
the contract and funding, we will collect clinical data before and
after ASCT identical to that collected and reported by other
investigators.
Inclusion criteria:
·A confirmed diagnosis of severe dcSSc, rapid skin progression with
TSS progression rate >20 modified Rodnan skin score units/year
(example: at ten months after onset of skin thickness by the
subject's history, the modified Rodnan skin score is 22, or
projected to be 26 after 12 months of skin disease). · Onset of skin
changes must have occurred within 2.5 years of study entry. · Age
between 18 and 70 years. · ECOG performance status of 0, 1 or 2 (but
not severly debilitated). · No immunosuppressive therapy, other than
corticosteroids, for at least four weeks prior to study entry. ·
Adequate organ function as manifested by: ANC>1500/mm 3 and
platelets > 50,000/mm 3 ; serum creatinine < 2.0 mg/dL and measured
creatinine clearance > 60 cc/min; bilirubin < 1.5 mg/dL, SGOT < 2x
normal; systolic ejection fraction documented by MUGA > 40%; and
both DLCO and FVC > 50% of predicted normal. · Absence of small
bowel malabsorption syndrome. · Willingness to participate in all
portions of the protocol, including pharmacodynamic and ancillary
immunological studies, and followup visits at this institution. ·
Written informed consent. · For females, negative pregnancy test,
non-lactating, and using effective means of contraception if of
childbearing potential. · No active infections (HIV negative by
serology, hepatitis C negative). · Absence of a history of a severe
personality disorder or severe mental illness.
Exclusion criteria:
Pregnant or breast feeding females or women of childbearing
potential not practicing birth control during and for two months
following treatment, or fertile and sexually active males unwilling
to use contraceptive techniques during and for two months following
treatment. · Known to be HIV positive, hepatitis C positive or have
another active infection. · Have a known medical or psychological
condition that would not permit completion of the trial. · Inability
or unwillingness to sign the informed consent document.
Primary outcome measure:
Non-hematologic toxicity experienced within three weeks after
transplant.
Secondary outcome measures:
Clinical and laboratory responses to chemotherapy/SCT determined at
12 and 24 months after transplant. Intrapatient analyses will be
performed to evaluate potential efficacy, although it is anticipated
that efficacy will be addressed formally in future randomized
trials.
Recruitment period:
A total of 15 subjects with SSc will be enrolled over a period of
approximately three years. IRB, GCRC and University of Pittsburgh
Medical Center approvals to begin recruitment were granted in
January 2003.
Completion:
Each participant will be followed for a minimum of two years and a
maximum of four years from the day he/she is entered into the study.
Date of expected analysis:
Two years after final study subject has completed ASCT.