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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Hodgkin Lymphoma, Non-Hodgkin's Lymphoma, Bone marrow transplant, stem cell transplant, busulfan, cyclophosphamide, etoposide

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama in Birmingham
  • Arizona Cancer Center
  • Alta Bates Summit Medical Center
  • Scripps Clinic
  • UCSD Medical Center BMT Program
  • Cedars-Sinai Medical Center
  • Sutter Cancer Center
  • University of California, Davis Medical Center
  • University of California San Francisco Medical Center
  • Rocky Mountain Cancer Centers
  • Florida Hospital Cancer Institute
  • Emory University
  • University of Illinois Cancer Center
  • The University of Chicago
  • Loyola University Chicago
  • Bone Marrow and Stem Cell Transplant Program
  • University of Kansas Medical Center
  • LSU Health Sciences Center at Shreveport/Feist Weiller Cancer Center
  • University of Maryland Medical Center - Marlene & Stewart Greenebaum Cancer Center
  • University of Michigan
  • University of Nebraska Medical Center
  • Montefiore-Einstein Cancer Center
  • Weill Cornell Medical College
  • University of North Carolina at Chapel Hill
  • Duke University Medical Center
  • University of Oklahoma Health Sciences Center
  • Oregon Health & Science University
  • The Western Pennsylvania Hospital
  • Medical University of South Carolina
  • Sarah Cannon Research Institute
  • Baylor University Medical Center
  • South Texas Veterans Health Care System
  • Texas Transplant Physician Group, PLLC
  • Huntsman Cancer Institute
  • Virginia Commonwealth University
  • Fred Hutchinson Cancer Research Center
  • West Virginia University Hospital
  • Saint John Regional Hospital
  • Queen Elizabeth II Health Sciences Centre - VG Site
  • The Ottawa Hospital
  • Royal Victoria Hospital MUHC
  • Saskatoon Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IV Busulfan

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Progression Events in 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

Number of Death Events in 2 Years.
The time of overall survival was defined as the time from transplantation to death of all causes.
Number of Transplant-related Death Events Until Day 100.
Transplant-related mortality was defined as death due to any cause other than disease relapse/progression up until Day 100.
Overall Response Rate
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.

Full Information

First Posted
July 28, 2009
Last Updated
July 1, 2014
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
Center for International Blood and Marrow Transplant Research
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1. Study Identification

Unique Protocol Identification Number
NCT00948090
Brief Title
PK-directed Dose Adjustment of IV Busulfan Conditioning Regimen for Autologous Stem Cell Transplant in Lymphoma Patients
Official Title
A Multi-center, Phase 2, Single-Arm, Open-Label Exploratory Study of Individually- Optimized Conditioning Using Pharmacokinetics [PK]-Directed Dose Adjustment of Once Daily Intravenous Busulfan, Followed by Autologous Hematopoietic Stem Cell Transplant in Subjects With Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
Center for International Blood and Marrow Transplant Research

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
Hodgkin Lymphoma, Non-Hodgkin's Lymphoma, Bone marrow transplant, stem cell transplant, busulfan, cyclophosphamide, etoposide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
207 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV Busulfan
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
IV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)
Intervention Description
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 Measure Information:
Title
Number of Progression Events in 2 Years.
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of Death Events in 2 Years.
Description
The time of overall survival was defined as the time from transplantation to death of all causes.
Time Frame
2 years
Title
Number of Transplant-related Death Events Until Day 100.
Description
Transplant-related mortality was defined as death due to any cause other than disease relapse/progression up until Day 100.
Time Frame
Day 100
Title
Overall Response Rate
Description
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.
Time Frame
Baseline, Day 100, Month 6, 12, 24, Early termination and End of Trial (within 30 days of the trial termination)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Agnes Elekes, MD
Organizational Affiliation
Otsuka Pharmaceutical Development and commercialization
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama in Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Alta Bates Summit Medical Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
UCSD Medical Center BMT Program
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Sutter Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Florida Hospital Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Illinois Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Chicago
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Bone Marrow and Stem Cell Transplant Program
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
LSU Health Sciences Center at Shreveport/Feist Weiller Cancer Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
University of Maryland Medical Center - Marlene & Stewart Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Montefiore-Einstein Cancer Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Western Pennsylvania Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
South Texas Veterans Health Care System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Texas Transplant Physician Group, PLLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
West Virginia University Hospital
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Saint John Regional Hospital
City
Saint John
State/Province
New Brunswick
ZIP/Postal Code
E2L 4L2
Country
Canada
Facility Name
Queen Elizabeth II Health Sciences Centre - VG Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Royal Victoria Hospital MUHC
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Saskatoon Cancer Centre
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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