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

Graft Versus Host Disease Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00454155
• Other study ID #: BPSC030
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 28, 2007
• Last updated: July 27, 2012
• Start date: February 2007
• Est. completion date: June 2010

Study information

• Verified date: May 2011
• Source: XOMA (US) LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 60 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
XOMA (US) LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to engraftment		100 days	No
Primary	Inflammatory markers		100 days	No
Primary	Inflammatory states		100 days	No
Primary	Transplant-related complications		100 days	Yes
Primary	The pharmacokinetics of opebacan		100 days	No