Clinical trial NCT00454155: Study of Opebacan in Patients Undergoing Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Official title: A Phase I/II Study of the Safety and Pharmacokinetics of Opebacan (rBPI21) in Patients Undergoing Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Graft Versus Host Disease
Keywords: HSCT
AGVHD
Myeloablative
Allogeneic
Hematopoietic
Stem
Cell
Transplantation
Lead sponsor: XOMA (US) LLC
Sponsor class: INDUSTRY
First posted: 2007-03-30
Enrollment: 6
Sex: ALL
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Time to engraftment
timeFrame: 100 days
measure: Inflammatory markers
timeFrame: 100 days
measure: Inflammatory states
timeFrame: 100 days
measure: Transplant-related complications
timeFrame: 100 days
measure: The pharmacokinetics of opebacan
timeFrame: 100 days
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Eva C Guinan, MD
role: PRINCIPAL_INVESTIGATOR
References: