A Phase I/II Study of the Safety and Pharmacokinetics of Opebacan (rBPI21) in Patients Undergoing Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
N/A
60 Years
Both
Graft Versus Host Disease
Trial Information
A Phase I/II Study of the Safety and Pharmacokinetics of Opebacan (rBPI21) in Patients Undergoing Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
IV infusion of opebacan to replace endogenous BPI during the peritransplant period will
result in the reduction of LPS-induced inflammatory sequelae, in particular aGvHD, in
patients undergoing allogeneic HSCT.
The rationale for using opebacan in patients undergoing myeloablative regimens and HSCT is
based on the following:
Endotoxemia has been demonstrated to play a central pathophysiologic role as a trigger of
aGvHD in animal models.
Endotoxemia following HSCT is associated with inflammatory conditions (such as inflammatory
cytokine release) that have been demonstrated in humans to be associated with organ damage
and increased morbidity and mortality.
Endotoxemia and LBP elevation have been demonstrated in humans undergoing ablative HSCT.
Chemotherapy-induced neutropenia results in a deficiency of endogenous BPI levels.
The timing of the endotoxemic insult is predictable (i.e., subsequent to myeloablative
chemotherapy and radiotherapy).
The return to normal neutrophil levels is not immediate and takes one week to several weeks.
Well established laboratory techniques for surrogate markers related to LPS presence and its
activities can facilitate the evaluation of molecules designed to inhibit or antagonize LPS
and its effects.
The objectives of this study are as follows:
To demonstrate the safety of escalating doses of opebacan in subjects undergoing
myeloablative allogeneic Hematopoietic Stem Cell Transplantation
To determine the pharmacokinetics of opebacan in subjects undergoing myeloablative
allogeneic Hematopoietic Stem Cell Transplantation
To determine if IV administration of opebacan is associated with changes in biological
markers for inflammation
To develop preliminary descriptive data on the occurrence and severity of Hematopoietic Stem
Cell Transplantation related complications, including aGvHD
Inclusion Criteria:
- Age <= 60 and undergoing allogeneic HSCT
- Life expectancy > 8 weeks
- Scheduled for treatment with a conditioning regimen intended to be myeloablative
- Female subjects of child-bearing age must have a negative urine pregnancy test.
Sexually active male and female subjects of reproductive age must be using a form of
contraception considered effective and medically acceptable by the Investigator.
Exclusion Criteria:
- Cumulative lifetime exposure of > 300 mg/M2 of anthracycline (expressed as
doxorubicin equivalent dose) or receipt of anthracycline within 180 days prior to
initiating conditioning for HSCT
- Active infection
- Prophylactic antibacterial antibiotics.
- Positive for HIV, HTLV-I, or HTLV-II
- Any prior stem cell transplant
- Prior history of CHF
- Cord blood is the source of a subject's transplanted cells.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Outcome Measure:
Time to engraftment
Outcome Time Frame:
100 days
Safety Issue:
No
Principal Investigator
Eva C Guinan, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
BPSC030
NCT ID:
NCT00454155
Start Date:
February 2007
Completion Date:
June 2010
Related Keywords:
- Graft Versus Host Disease
- HSCT
- AGVHD
- Myeloablative
- Allogeneic
- Hematopoietic
- Stem
- Cell
- Transplantation
- Graft vs Host Disease
Name | Location |
|---|---|
| Boston, Massachusetts |
