Clinical trial NCT00223730: Chemotherapy Toxicity Reduction Via Urea Cycle Support
Official title: Chemotherapy Toxicity Reduction Via Urea Cycle Support
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: Peripheral Blood Stem Cell Transplant
Bone Marrow Transplant
Citrulline
Urea Cycle
Hepatic Injury
Allogeneic PBSCT
Matched-Unrelated PBSCT
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2005-09-22
Enrollment: 100
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Brian W. Christman, MD
role: PRINCIPAL_INVESTIGATOR
References: