Chemotherapy Toxicity Reduction Via Urea Cycle Support

NCT ID: NCT00223730

Last Updated: 2016-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2007-12-31

Brief Summary

Patients undergoing bone marrow transplantation (BMT) and peripheral blood stem cell transplants (PBSCT) frequently develop organ dysfunctions, much of which may be initiated by damage to the liver and to cells lining blood vessels.

We, the researchers at Vanderbilt University, propose to perform a randomized, prospective, double-blind, placebo-controlled study of 144 patients undergoing allogeneic marrow transplantation. The treatment is aimed at supporting hepatic urea cycle function in patients receiving escalated dose chemotherapy/BMT. By so doing we hope to prevent development of hepatic venoocclusive disease (HVOD) and acute lung injury (ALI), two morbid complications of BMT. Patients will be randomized to receive oral citrulline, a urea cycle amino acid intermediate, or placebo beginning before conditioning therapy and continuing until 21 days after BMT. All patients will be followed for 100 days after study enrollment with intensive data collection.

Conditions

Cancer

Keywords

Peripheral Blood Stem Cell Transplant; Bone Marrow Transplant; Citrulline; Urea Cycle; Hepatic Injury; Allogeneic PBSCT; Matched-Unrelated PBSCT

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

citrulline

Patients randomized to receive oral citrulline at 3.8 gm/m2 in split BID dosing

Group Type: EXPERIMENTAL

Citrulline

Intervention Type: DRUG

Oral provision of amino acid citrulline to support impaired urea cycle function during escalated dose chemotherapy for stem cell transplant

Placebo

Patients randomized to receive oral diluent for citrulline in BID dosing

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Citrulline

Oral provision of amino acid citrulline to support impaired urea cycle function during escalated dose chemotherapy for stem cell transplant

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• We propose to study 144 patients undergoing allogeneic bone marrow transplantation or peripheral blood stem cell transplant over a 4 year period.
• Patients of either sex and of any race or ethnic origin, older than age greater than or equal to13, and admitted to the Myelosuppression Unit (MSU) of Vanderbilt University Hospital or the VA Hospital to undergo bone marrow transplantation will be recruited for this study.

Exclusion Criteria

• Patients will be excluded if pregnant (unlikely) or if informed consent cannot be obtained.
• Because of the intrinsic toxicity of the treatment regimens, BMT is not usually offered to patients with severe underlying derangements in organ function. Nevertheless, other exclusions that will prevent entry of patients into the study include advanced renal or hepatic failure (serum creatinine > 6mg/dl, serum bilirubin >3.5 mg/dl), moribund patients, and patients whose primary physician is not committed to full support of the patient (i.e. "Do Not Resuscitate").
• Other exclusions will include patients enrolled in another experimental (interventional) protocol aimed at reducing transplant related complications during BMT, patients testing positive for HIV, those who have had previous BMT, and patients actively bleeding at the time of initiation of induction therapy. We will not exclude patients undergoing newer regimens of cytotoxic chemotherapy.

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Brian Christman

Professor of Medicine and Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian W. Christman, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

NIH HL-55198

Identifier Type: OTHER

Identifier Source: secondary_id

NIH 1P-30CA68485

Identifier Type: OTHER

Identifier Source: secondary_id

NIH 1RO1-CA092313-01

Identifier Type: OTHER

Identifier Source: secondary_id

990675

Identifier Type: -

Identifier Source: org_study_id