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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00948090
• Other study ID #: 273-08-201
• Status: Completed
• Phase: Phase 2
• First received: July 28, 2009
• Last updated: July 1, 2014
• Start date: January 2010
• Est. completion date: June 2013

Study information

• Verified date: July 2014
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 207
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Center for International Blood and Marrow Transplant Research

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years	No
Secondary	Number of Death Events in 2 Years.	The time of overall survival was defined as the time from transplantation to death of all causes.	2 years	No
Secondary	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.	Day 100	No
Secondary	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.	Baseline, Day 100, Month 6, 12, 24, Early termination and End of Trial (within 30 days of the trial termination)	No