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

This study has been terminated.
(Lack of enrollment)
Sponsor:
Information provided by (Responsible Party):
XOMA (US) LLC
ClinicalTrials.gov Identifier:
NCT00454155
First received: March 28, 2007
Last updated: July 27, 2012
Last verified: May 2011
  Purpose

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 Intervention Phase
Graft Versus Host Disease
Drug: Opebacan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by XOMA (US) LLC:

Primary Outcome Measures:
  • Time to engraftment [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Inflammatory markers [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Inflammatory states [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Transplant-related complications [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • The pharmacokinetics of opebacan [ Time Frame: 100 days ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: February 2007
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00454155

Locations
United States, Massachusetts
Boston, Massachusetts, United States
Sponsors and Collaborators
XOMA (US) LLC
Investigators
Principal Investigator: Eva C Guinan, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: XOMA (US) LLC
ClinicalTrials.gov Identifier: NCT00454155     History of Changes
Other Study ID Numbers: BPSC030
Study First Received: March 28, 2007
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by XOMA (US) LLC:
HSCT
AGVHD
Myeloablative
Allogeneic
Hematopoietic
Stem
Cell
Transplantation

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases

ClinicalTrials.gov processed this record on August 28, 2014