Study of Opebacan in Patients Undergoing Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Sponsor

XOMA (US) LLC (Industry)

Overall Status

Terminated

CT.gov ID

NCT00454155

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Drug: Opebacan	Phase 1/Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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 Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Opebacan	Drug: Opebacan 4 mg/kg continuous IV infusion for 30 minutes followed immediately by 6 mg/kg/day continuous IV infusion for 3 days

Arm

Intervention/Treatment

Experimental: Opebacan

Drug: Opebacan

4 mg/kg continuous IV infusion for 30 minutes followed immediately by 6 mg/kg/day continuous IV infusion for 3 days

Outcome Measures

Primary Outcome Measures

Time to engraftment [100 days]
Inflammatory markers [100 days]
Inflammatory states [100 days]
Transplant-related complications [100 days]
The pharmacokinetics of opebacan [100 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.