Scleroderma: Cyclophosphamide or Transplantation (SCOT) Substudy 03

Status:	Completed
Conditions:	Neurology, Dermatology
Therapuetic Areas:	Dermatology / Plastic Surgery, Neurology
Healthy:	No
Age Range:	Any
Updated:	2/4/2013
Start Date:	March 2009
End Date:	March 2016
Contact:	Keith Sullivan, MD
Email:	sulli025@mc.duke.edu
Phone:	866-909-SCOT

Mechanistic Study: Molecular Analysis of T Cell Immune Recovery for the SCOT Trial

Production of broadly reactive T cells and maintenance of a diverse peripheral T cell
repertoire are critical to the success of the human immune system. Cyclophosphamide
treatment and preparative high-dose immunosuppressive therapy prior to stem cell
transplantation in the SCOT trial are anticipated to have a significant impact on
thymopoiesis and the peripheral TCR repertoire. The overall implications of this
mechanistic study are a better understanding of the impact of these therapeutic and
preparative approaches on adult thymopoiesis, and the kinetics and breadth of T cell immune
recovery in subjects undergoing stem cell transplantation.

Thirty subjects will be enrolled from each treatment arm of the SCOT trial, which is an
interventional, Phase II/III study for individuals with systemic sclerosis who are
randomized to receive either high dose immunosuppressive therapy (HDIT) followed by
autologous stem cell transplantation or monthly high dose intravenous cyclophosphamide (the
latter for 12 monthly cycles).

Peripheral blood measures of T cell reconstitution will be assessed before and after
completion of randomized therapy.

The purpose of this mechanistic 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 (CY) and high-dose immunosuppressive therapy with autologous peripheral
blood stem cell transplantation (HDIT-transplantation) on thymopoiesis, and [3] to describe
the kinetics and breadth of T cell immune recovery in SSc patients treated with
HDIT-transplantation.

Recruitment for this study will be limited to participants who have elected to participate
in the SCOT study and have been randomized to one of the SCOT treatment arms. Participants
will be recruited after randomization to ensure balance on the two arms for this mechanistic
study and must agree to participate and sign an informed consent for this mechanistic study
prior to initiation of treatment on either arm. Sixty participants, 30 from each arm, will
be recruited for this sub-study. It will be conducted at the participating SCOT transplant
centers.

Peripheral blood samples will be collected (20 mL) pre-treatment (prior to first infusion
for cyclophosphamide arm or mobilization for transplant arm) and approximately 6, 12, 24,
36, and 48 months post completion of treatment to be aligned with the regularly scheduled
SCOT protocol visits. Specific measures will be the level of peripheral blood T Cell
Receptor Excision Circles (sjTREC) and peripheral blood T cell receptor Vbeta repertoire
diversity before and after completion of randomized therapy.

Inclusion Criteria:

- Participation in DAIT SCSSc-01 (SCOT Trial)

Exclusion Criteria:

- No additional exclusion criteria

We found this trial at

sites

UCLA Medical School

Los Angeles, California 90095

from

Los Angeles, CA