Mobilization of Stem Cells With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma Patients

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00103610
First received: February 11, 2005
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to determine whether the combination of AMD3100 (plerixafor) and granulocyte colony-stimulating factor (G-CSF or generic name filgrastim) is better than G-CSF alone to mobilize and collect the optimal number of stem cells in non-Hodgkin's lymphoma patients for autologous transplantation.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Drug: Granulocyte colony-stimulating factor plus plerixafor
Drug: Granulocyte colony-stimulating factor plus placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative Trial of AMD3100 Plus G-CSF Versus G-CSF Plus Placebo to Mobilize and Collect ≥ 5 * 10^6 CD34+ Cells/kg in Non-Hodgkin's Lymphoma Patients for Autologous Transplantation

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Proportion of Participants Able to Achieve Target (≥ 5*10^6 CD34+ Cells/kg) in 4 or Fewer Days of Apheresis [ Time Frame: Days 5 to 8 ] [ Designated as safety issue: No ]
    Proportion of participants achieving a target of ≥ 5*10^6 CD34+ cells/kg in 4 or fewer days of apheresis. Central lab data were taken from Days 5 to 8 of the Treatment/Apheresis period. Each participant's value was calculated as the sum of all daily values collected over the 4 apheresis days.


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: up to Day 38 ] [ Designated as safety issue: Yes ]
    Number of participants with treatment emergent adverse events (AEs). The timeframe for treatment emergent AEs is defined as Day 1 (start of G-CSF Mobilization) to the day before starting chemotherapy (approximately 38 days later). AEs were reported regardless of relationship to study treatment. The investigator graded each AE using the World Health Organization (WHO) Adverse Event Grading Scale. AEs of Grade 3 were considered severe and Grade 4 were considered life-threatening.

  • Proportion of Participants Able to Achieve Target (>=2*10^6 CD34+ Cells/kg) in 4 or Fewer Days of Apheresis [ Time Frame: up to Day 8 ] [ Designated as safety issue: No ]
    Proportion of participants achieving a target of >=2*10^6 CD34+ Cells/kg in 4 or fewer days of apheresis. Central lab data were taken from Days 5 to 8 of the Treatment/Apheresis period. Each participant's value was calculated as the sum of all daily values collected over the 4 apheresis days.

  • Median Number of Days of Apheresis Required to Achieve >=5*10^6 CD34+ Cells/kg [ Time Frame: up to Day 8 ] [ Designated as safety issue: No ]
    The Kaplan Meier estimate of median number of days (number of days at which 50% of participants reached the threshold, accounting for censored values) in each treatment arm to collect the target number of cells (≥5*10^6 CD34+ cells/kg) for transplantation. Central laboratory values were used.

  • Median Number of Days to Polymorphonuclear (PMN) Cell Engraftment [ Time Frame: Up to Month 13 ] [ Designated as safety issue: No ]
    The Kaplan Meier estimate of median number of days to PMN engraftment (number of days at which 50% of participants have experienced the event, accounting for censored values) was a secondary efficacy endpoint. Engraftment was defined as PMN counts ≥ 0.5*10^9/L for 3 consecutive days or ≥ 1.0*10^9/L for 1 day. Time to engraftment corresponded to the first day that the criteria were met.

  • Median Number of Days to Platelet (PLT) Engraftment [ Time Frame: Up to Month 13 ] [ Designated as safety issue: No ]
    The Kaplan Meier estimate of median number of days to PLT engraftment (number of days at which 50% of participants have experienced the event, accounting for censored values) was a secondary efficacy endpoint. Engraftment was defined as ≥ 20*10^9/L without transfusion for the preceding 7 days. Time to engraftment corresponded to the first day that the criteria were met.

  • Graft Durability at 100 Days Post Transplantation [ Time Frame: approximately Day 138 ] [ Designated as safety issue: No ]
    The proportion of participants maintaining a durable graft at 100 days post transplantation by at least 2 of the following criteria (without erythropoietin (EPO), G-CSF, or transfusions): (1) a platelet count >50000/µL without transfusion for at least 2 weeks, (2) hemoglobin >=10g/dL for at least 1 month, (3) and absolute neutrophil count >1000/µL for at least 1 week.

  • Graft Durability at 6 Months Post Transplantation [ Time Frame: approximately Month 7 ] [ Designated as safety issue: No ]
    The proportion of participants maintaining a durable graft at 6 months post transplantation by at least 2 of the following criteria (without erythropoietin (EPO), G-CSF, or transfusions): (1) a platelet count >50000/µL without transfusion for at least 2 weeks, (2) hemoglobin >=10g/dL for at least 1 month, (3) and absolute neutrophil count >1000/µL for at least 1 week.

  • Graft Durability at 12 Months Post Transplantation [ Time Frame: approximately Month 13 ] [ Designated as safety issue: No ]
    The proportion of participants maintaining a durable graft 12 months post-transplantation by at least 2 of the following criteria (without erythropoietin (EPO), G-CSF, or transfusions): (1) a platelet count >50000/µL without transfusion for at least 2 weeks, (2) hemoglobin >=10g/dL for at least 1 month, (3) and absolute neutrophil count >1000/µL for at least 1 week.


Enrollment: 298
Study Start Date: January 2005
Study Completion Date: December 2007
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: G-CSF plus plerixafor Drug: Granulocyte colony-stimulating factor plus plerixafor
Participants underwent mobilization with granulocyte colony-stimulating factor (G-CSF) (10 µg/kg/day) for 4 days, administered by subcutaneous (SC) injection. On the evening of Day 4, participants received plerixafor (240 µg/kg), administered by SC injection. On Day 5, participants received a morning dose of G-CSF (10 µg/kg) and underwent apheresis approx. 10 to 11 hours after the dose of plerixafor (within 60 minutes of G-CSF administration). Participants continued to receive an evening dose of plerixafor followed by a morning dose of G-CSF and apheresis for up to 4 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected. Participants who participated in the rescue procedure underwent an additional daily treatment with plerixafor (240 µg/kg) and apheresis for up to 4 days.
Other Names:
  • AMD3100
  • Mozobil
Placebo Comparator: G-CSF plus placebo Drug: Granulocyte colony-stimulating factor plus placebo
Participants underwent mobilization with granulocyte colony-stimulating factor (G-CSF) (10 µg/kg/day) for 4 days, administered by subcutaneous (SC) injection. On the evening of Day 4, participants received placebo, administered by SC injection. On Day 5, participants received a morning dose of G-CSF (10 µg/kg) and underwent apheresis approx. 10 to 11 hours after the dose of placebo (within 60 minutes of G-CSF administration). Participants continued to receive an evening dose of placebo followed by a morning dose of G-CSF and apheresis for up to 4 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected. Participants who participated in the rescue procedure underwent an additional daily treatment with plerixafor (240 µg/kg) and apheresis for up to 4 days.

Detailed Description:

A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Currently filgrastim (G-CSF), a colony stimulating factor, is used to cause the growth and mobilization of stem cells from bone marrow to peripheral blood, which can then be collected from the peripheral blood by a process called apheresis. Plerixafor aids in the release of the stem cells from the bone marrow into the peripheral blood, possibly allowing for a more rapid collection of a larger number of stem cells from the peripheral blood. Larger stem cell doses for transplantation correlate to faster recovery times after high dose chemotherapy followed with stem cell transplantation. This study is intended to determine whether the combination of plerixafor with filgrastim is better than filgrastim alone in helping non-Hodgkin's lymphoma patients collect at least 5 million stem cells in four or less apheresis sessions.

This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (Abbreviated List):

  • Non-Hodgkin's lymphoma in first or second complete or partial remission
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • White Blood Cell count (WBC) > 2.5*10^9/L
  • Platelet (PLT) > 100*10^9/L

Exclusion Criteria (Abbreviated List):

  • Failed previous stem cell collection
  • Prior autologous or allogeneic transplant
  • Brain metastases or bone marrow involvement > 20%
  • Radiation to pelvis
  • Abnormal electrocardiogram (ECG) with rhythm disturbance (ventricular arrhythmias) or other conduction abnormality
  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: NCT00103610

  Hide Study Locations
Locations
United States, Arizona
City of Hope Samaritan Bone Marrow Transplant Program
Phoenix, Arizona, United States, 85006
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
Shands Teaching Hospital, University of Florida
Gainesville, Florida, United States, 32610
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Indiana
Indiana Blood and Marrow Transplantation Center
Beech Grove, Indiana, United States, 46107
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City Cancer Center
Kansas City, Missouri, United States, 64111
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Medical Center: Clarkson and University Hospitals
Omaha, Nebraska, United States, 68198
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Wilford Hall Medical Center
Lackland AFB, Texas, United States, 78236
University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Additional Information:
Publications:
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00103610     History of Changes
Obsolete Identifiers: NCT00248508
Other Study ID Numbers: AMD3100-3101
Study First Received: February 11, 2005
Results First Received: February 6, 2009
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Sanofi:
Non-Hodgkin's lymphoma
Stem cell mobilization

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
JM 3100
Lenograstim
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014