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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: IV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)

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.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre - VG Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital MUHC
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama in Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Arizona Cancer Center
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • La Jolla, California, United States, 92093
      • UCSD Medical Center BMT Program
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University Of Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois Cancer Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Bone Marrow and Stem Cell Transplant Program
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center at Shreveport/Feist Weiller Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center - Marlene & Stewart Greenebaum Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore-Einstein Cancer Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina At Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • The Western Pennsylvania Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • San Antonio, Texas, United States, 78229
      • South Texas Veterans Health Care System
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Physician Group, PLLC
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV Busulfan; 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	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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)

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Center for International Blood and Marrow Transplant Research
• Investigators: Study Director: Agnes Elekes, MD, Otsuka Pharmaceutical Development and Commercialization

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 28, 2009
• First Submitted That Met QC Criteria: July 28, 2009
• First Posted (Estimate): July 29, 2009

Study Record Updates

• Last Update Posted (Estimate): July 31, 2014
• Last Update Submitted That Met QC Criteria: July 1, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: stem cell transplant; cyclophosphamide; Non-Hodgkin's Lymphoma; Bone marrow transplant; etoposide; busulfan; Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Etoposide; Busulfan
• Other Study ID Numbers: 273-08-201