PK-directed Dose Adjustment of IV Busulfan Conditioning Regimen for Autologous Stem Cell Transplant in Lymphoma Patients

Phase 2

Completed

Conditions: Lymphoma

Interventions: Drug: IV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)

Registration Number: NCT00948090

Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary: This is a study for the outcome and safety of individualized busulfan dosing with cyclophosphamide and etoposide for patients preparing for a stem cell transplant to treat Non-Hodgkin or Hodgkin's Lymphoma.

Detailed Description: Evaluation of progression-free survival, transplant related mortality, overall survival, and overall response rate, in subjects with NHL and HL receiving an IV busulfan-based conditioning regimen with PK-guided IV busulfan dosing, followed by autologous HSCT as well as comparison to those receiving carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning regimen (and its variants) obtained from registry data in the Center for International Blood and Marrow Transplant Research (CIBMTR) Assessment of the safety profile of a BuCyE conditioning regimen with PK-directed dosing of IV busulfan will also be completed.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 207

Inclusion Criteria

Subjects with NHL to be included:

Any subject with NHL that had relapsed or progressed following initial therapy with an anthracycline-based chemotherapy regimen and has achieved a subsequent partial remission (PR) or a complete remission (CR) following a salvage chemotherapy regimen.
Any subject with NHL that was initially refractory to an anthracycline-based chemotherapy regimen but who has achieved a PR or CR following a salvage chemotherapy regimen.
Any subject with an initial International Prognostic Index (IPI) score 4-5 who achieved a PR or any CR following an anthracycline-based chemotherapy regimen except subjects with Mantle cell, T cell and Natural Killer (NK) cell pathologies.
Subjects with Mantle cell, T cell and NK cell lymphoma may be enrolled if they have PR or CR after initial therapy.
Any subject that has relapsed or progressed following previous autologous HSCT.

Subjects with HL to be included:

Any subject with HL that had relapsed or progressed following initial therapy with an multi-drug chemotherapy regimen and has achieved a subsequent PR or a CR following a salvage chemotherapy regimen.
Any subject with HL that is initially refractory to a multi-drug chemotherapy regimen but who has achieved a PR or CR following a salvage chemotherapy regimen.
Any subject that has relapsed or progressed following previous autologous HSCT.

Exclusion Criteria

Any subject with chemoresistant disease by demonstration of less than PR to most recent chemotherapy, and any subject with prior treatment history of autologous HSCT or high-dose chemotherapy with stem cell rescue for any medical reason will be excluded.

Excluded will also be subjects with existing or active central nervous system lymphoma or human immunodeficiency virus related lymphoma, unacceptable organ function, or uncontrolled infections.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IV Busulfan	IV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)	Pk-directed IV Busulfan (based on test dose method) for 4 days followed by Etoposide 1400mg/m2 QD for one day and Cyclophosphamide 2.5 g/m2 QD for two days followed by autologous stem cell transplant

Primary Outcome Measures

Name	Time	Method
Number of Progression Events in 2 Years.	2 years	The time of Progression-Free Survival (PFS) was defined as the time from transplantation to the occurrence of the event that was death or first recurrence of progressive disease.

Secondary Outcome Measures

Name	Time	Method
Number of Death Events in 2 Years.	2 years	The time of overall survival was defined as the time from transplantation to death of all causes.
Overall Response Rate	Baseline, Day 100, Month 6, 12, 24, Early termination and End of Trial (within 30 days of the trial termination)	The overall response status is complete response and not complete response (partial remission, primary refractory/primary induction failure, stable disease, progressive disease, and relapse) at Baseline and each of the scheduled follow-up time points.
Number of Transplant-related Death Events Until Day 100.	Day 100	Transplant-related mortality was defined as death due to any cause other than disease relapse/progression up until Day 100.

Trial Locations

Locations (42): UCSD Medical Center BMT Program
🇺🇸
La Jolla, California, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
The Ottawa Hospital
🇨🇦
Ottawa, Ontario, Canada
Royal Victoria Hospital MUHC
🇨🇦
Montreal, Quebec, Canada
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Emory University
🇺🇸
Atlanta, Georgia, United States
The University of Chicago
🇺🇸
Chicago, Illinois, United States
University of Maryland Medical Center - Marlene & Stewart Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
West Virginia University Hospital
🇺🇸
Morgantown, West Virginia, United States
LSU Health Sciences Center at Shreveport/Feist Weiller Cancer Center
🇺🇸
Shreveport, Louisiana, United States
Montefiore-Einstein Cancer Center
🇺🇸
Bronx, New York, United States
The Western Pennsylvania Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Queen Elizabeth II Health Sciences Centre - VG Site
🇨🇦
Halifax, Nova Scotia, Canada
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Loyola University Chicago
🇺🇸
Maywood, Illinois, United States
Alta Bates Summit Medical Center
🇺🇸
Berkeley, California, United States
University of Illinois Cancer Center
🇺🇸
Chicago, Illinois, United States
Scripps Clinic
🇺🇸
La Jolla, California, United States
Weill Cornell Medical College
🇺🇸
New York, New York, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
University of Alabama in Birmingham
🇺🇸
Birmingham, Alabama, United States
Sutter Cancer Center
🇺🇸
Sacramento, California, United States
University of California, Davis Medical Center
🇺🇸
Sacramento, California, United States
University of California San Francisco Medical Center
🇺🇸
San Francisco, California, United States
South Texas Veterans Health Care System
🇺🇸
San Antonio, Texas, United States
Texas Transplant Physician Group, PLLC
🇺🇸
San Antonio, Texas, United States
Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Rocky Mountain Cancer Centers
🇺🇸
Denver, Colorado, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Bone Marrow and Stem Cell Transplant Program
🇺🇸
Indianapolis, Indiana, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
Saint John Regional Hospital
🇨🇦
Saint John, New Brunswick, Canada
Florida Hospital Cancer Institute
🇺🇸
Orlando, Florida, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
University of Kansas Medical Center
🇺🇸
Westwood, Kansas, United States