MDACC Study Summary 2006-0116 (Archived)

Study Summary
No. 2006-0116:.......Blood And Marrow Transplantation......Sergio A. Giralt......Stem Cell Transplantation and Cellular Therapy

Study Summary Title



Study Summary Number:	2006-0116

Study Title:	Defibrotide For The Treatment Of Severe Hepatic Veno-Occlusive Disease In Hematopoietic Stem Cell Transplant Patients: A Historically-Controlled, Multi-Center Phase 3 Study To Determine Safety & Efficacy

Physician

New Patient Referral



Name:	Sergio A. Giralt	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Stem Cell Transplantation and Cellular Therapy	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-5745 Contact us about clinical trials

General Information



Disease Group:	Blood And Marrow Transplantation	Supported By:	N/A

Phase of Study:	Phase III	Return Visit:	At least weekly from discharge to day 100 post SCT

Treatment Agents:	Difibrotide New Testing Agent	Home Care:	n/a

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	30 days


Description/ Intervention:	The goal of this clinical research study is to learn the effectiveness of defibrotide in the treatment of patients with severe hepatic VOD. The safety of this treatment will also be studied.

Study Objectives / Outcomes

Primary
1. The primary objective is to demonstrate the efficacy of Defibrotide (DF) in patients
with severe VOD in terms of Complete Response of VOD (bilirubin less than 2
mg/dL and resolution of MOF) by Day + 100 post SCT as the primary parameter.

Secondary
1. to compare survival at 100 days and 6 months following SCT in patients receiving
Defibrotide to those in a Historical Control who did not receive defibrotide;
2. to assess the safety of the selected dose and schedule;
3. to collect and bank samples prior to and during therapy for special studies of
potential serum and endothelial markers for VOD;
4. to collect historical information about the treatment centers, including severe VOD
treatment across hospitals and over time and number and type of transplants per
year.

Study Status Information



Study Activation / Registration Date:	09/26/2006

IRB Review and Approval Date:	08/02/2006

Study Type:	Phase Iii

Recruitment Status:	Terminated

Projected Accrual:	80

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients who meet both of the following criteria will be enrolled in the treatment and historical control groups: Clinical diagnosis of VOD, defined by jaundice (bilirubin > 2 mg/dL) and at least 2 of the following clinical findings, by Day +21 post stem cell transplant: ascites, weight gain > 5% above baseline weight, hepatomegaly Severe VOD, defined as VOD with multi-organ failure (MOF), i.e., presence of one or both of the following, by Day +28 post stem cell transplant: renal dysfunction: pulmonary dysfunction: documentation of oxygen saturation < 90% on room air .

2) Patients to be enrolled in the treatment group must also provide voluntary written informed consent to the protocol to be eligible for the study. For minor patients, parent/legal guardian will provide consent and, when possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent. For patients in the historical control group, informed consent from each patient is not required by the Sponsor as part of this study; however, investigators must comply with the requirements of their own IRB.

Exclusion Criteria:

1) Documentation of pre-existing (at the time of SCT) cirrhosis of the liver.

2) An alternative diagnosis for ascites, weight gain and jaundice, such as fulminant viral hepatitis, at the time that severe VOD criteria are met.

3) Documented diagnosis of GVHD, grade B-D according to the IBMTR Severity Index (see Appendix B), involving the liver or gut, or documented diagnosis of GVHD, grade C or higher according to the IBMTR Severity Index, involving skin. Please note: 1. Patients with grade B GVHD involving only skin are eligible. 2. Grade is established without consensus grading (i.e., downgrading) for the purpose of this study.

4) Prior solid organ transplant

5) Dependence on dialysis or oxygen supplementation at the time of SCT.

6) Use of any medication which increases the risk of hemorrhage. Use of heparin or other anticoagulants within 12 hours unless being used for routine central venous line management, fibrinolytic instillation for central venous line occlusion, intermittent dialysis or ultrafiltration of CVVH

7) Clinically significant uncontrolled acute bleeding, defined as hemorrhage requiring > 15 cc/kg of packed red blood cells to replace blood loss, OR bleeding from a site which in the Investigator's opinion constitutes a potential life-threatening source (e.g. pulmonary hemorrhage or CNS bleeding), irrespective of amount of blood loss, at any point from the date of SCT through the date of severe VOD diagnosis. Please note: Transfusion of these amounts in the absence of clinically significant uncontrolled acute bleeding is not a contraindication to enrollment.

8) Hemodynamic instability as defined by a requirement for multiple pressors, or inability to maintain mean arterial pressure within 1 standard deviation of age-adjusted levels (see Appendix C) with single pressor support. Please note: 1. Patients on a single pressor must have stable mean arterial pressure for at least 8 hours. 2. Patients requiring renal dose dopamine alone (2-5 mcg/kg/min) are eligible without measurement of mean arterial pressure.

9) Prior therapy with defibrotide.

Links

Registration Number: NCT00358501
Study Information on Clinical Trials Registry (clinicaltrials.gov)