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Mechanistic Study: Pharmokinetics of 4-hydroxycyclophosphamide in Patients Receiving Cyclophosphamide for the SCOT Trial


Phase 2/Phase 3
18 Years
69 Years
Open (Enrolling by invite only)
Both
Scleroderma, Systemic, Sclerosis

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Trial Information

Mechanistic Study: Pharmokinetics of 4-hydroxycyclophosphamide in Patients Receiving Cyclophosphamide for the SCOT Trial


The purpose of this study is to determine the plasma concentration and exposure time
required for cyclosphosphamide to produce optimal immunosuppressive activity with minimal
toxicity in subjects with severe systemic sclerosis.

Secondary objectives are:

1. To determine whether the initial cyclophosphamide exposure affects the pharmacokinetics
of a second dose in the cyclophosphamide arm.

2. To evaluate the effect of this high dose cyclophosphamide regimen on myelosuppression
as assessed by total white cell count and that of polymorphic mononuclear cells at
approximately 24 and 48 hours post-dose in the transplant arm.

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. Fifty participants, 25 from each arm, will
be recruited for this sub-study. It will be conducted at the participating SCOT transplant
and rheumatology centers.

In Arm 1 (the transplant arm), as part of the conditioning regimen, cyclophosphamide at a
dose of 60 mg/kg will be infused over 1 to 2 hours (on 2 consecutive days), and blood
collection will occur prior to dosing and at Hours 2, 4, 6, 8, 10, and 23 after completion
of the first infusion for measurement of 4-OH-CP pharmacokinetics. Additionally, blood
collection will occur at approximately 24 and 48 hours in the transplant arm to obtain white
cell count and differential (including polymorphic mononuclear cell counts).

In Arm 2 (the high-dose cyclophosphamide arm), an initial cyclophosphamide dose of 500 mg/m2
will be infused over 1 to 2 hours, and blood collection will occur prior to dosing and at
Hours 0.5, 1, 2, and 24 after completion of drug infusion for measurement of 4-OH-CP
pharmacokinetics. For the second monthly infusion, a cyclophosphamide dose of 750 mg/m2 will
be infused with blood collection occurring at the same time points as those for the first
dose.


Inclusion Criteria:



- Participation in DAIT SCSSc-01 (SCOT Trial)

Exclusion Criteria:

- No additional exclusion criteria

Type of Study:

Observational

Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

Plasma concentration and exposure time required for cyclosphosphamide to produce optimal immunosuppressive activity with minimal toxicity

Outcome Time Frame:

Throughout study

Safety Issue:

No

Principal Investigator

David J. Adams, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Duke University

Authority:

United States: Food and Drug Administration

Study ID:

DAIT SCSSc-01 -01

NCT ID:

NCT00848614

Start Date:

January 2008

Completion Date:

June 2012

Related Keywords:

  • Scleroderma, Systemic
  • Sclerosis
  • Scleroderma, Systemic
  • Scleroderma, Diffuse
  • Scleroderma, Localized
  • Sclerosis

Name

Location

University of MichiganAnn Arbor, Michigan  48109-0624
Medical College of WisconsinMilwaukee, Wisconsin  53226
Boston University School of MedicineBoston, Massachusetts  02118
City of Hope National Medical CenterLos Angeles, California  91010
University of Tennessee, MemphisMemphis, Tennessee  38163
Duke UniversityDurham, North Carolina  27710
University of KentuckyLexington, Kentucky  40536-0098
University of WisconsinMadison,, Wisconsin  53792-5666
UCLA Medical SchoolLos Angeles, California  90095-1670
University of Texas-Houston Medical SchoolHouston, Texas  77030
Fred Hutchinson Cancer Research Center (FHCRC)Seattle, Washington  98109