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

This study has been completed.
Sponsor:
Collaborator:
Center for International Blood and Marrow Transplant Research
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00948090
First received: July 28, 2009
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: IV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Number of Progression Events in 2 Years. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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. [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
    Transplant-related mortality was defined as death due to any cause other than disease relapse/progression up until Day 100.

  • Overall Response Rate [ Time Frame: Baseline, Day 100, Month 6, 12, 24, Early termination and End of Trial (within 30 days of the trial termination) ] [ Designated as safety issue: No ]
    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.


Enrollment: 207
Study Start Date: January 2010
Study Completion Date: June 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948090

  Show 42 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Center for International Blood and Marrow Transplant Research
Investigators
Study Director: Agnes Elekes, MD Otsuka Pharmaceutical Development and commercialization
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00948090     History of Changes
Other Study ID Numbers: 273-08-201
Study First Received: July 28, 2009
Results First Received: May 21, 2014
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Hodgkin Lymphoma
Non-Hodgkin's Lymphoma
Bone marrow transplant
stem cell transplant
busulfan
cyclophosphamide
etoposide

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Busulfan
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014