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

Lymphoma, Non-Hodgkin Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103610
• Other study ID #: AMD3100-3101
• Status: Completed
• Phase: Phase 3
• First received: February 11, 2005
• Last updated: February 10, 2014
• Start date: January 2005
• Est. completion date: December 2007

Study information

• Verified date: February 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00248508

Recruitment information / eligibility

• Status: Completed
• Enrollment: 298
• Est. completion date: December 2007
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	Indiana Blood and Marrow Transplantation Center	Beech Grove	Indiana
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Shands Teaching Hospital, University of Florida	Gainesville	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Kansas City Cancer Center	Kansas City	Missouri
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Nebraska Medical Center: Clarkson and University Hospitals	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	City of Hope Samaritan Bone Marrow Transplant Program	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Texas Transplant Institute	San Antonio	Texas
United States	University of Texas Health Science Center	San Antonio	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Washington University School of Medicine	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E, Nademanee A, McCarty J, Bridger G, Calandra G; 3101 Investigators. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimula — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Able to Achieve Target (= 5*10^6 CD34+ Cells/kg) in 4 or Fewer Days of Apheresis	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.	Days 5 to 8	No
Secondary	Number of Participants With Adverse Events	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.	up to Day 38	Yes
Secondary	Proportion of Participants Able to Achieve Target (>=2*10^6 CD34+ Cells/kg) in 4 or Fewer Days of Apheresis	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.	up to Day 8	No
Secondary	Median Number of Days of Apheresis Required to Achieve >=5*10^6 CD34+ Cells/kg	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.	up to Day 8	No
Secondary	Median Number of Days to Polymorphonuclear (PMN) Cell Engraftment	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.	Up to Month 13	No
Secondary	Median Number of Days to Platelet (PLT) Engraftment	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.	Up to Month 13	No
Secondary	Graft Durability at 100 Days Post Transplantation	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.	approximately Day 138	No
Secondary	Graft Durability at 6 Months Post Transplantation	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.	approximately Month 7	No
Secondary	Graft Durability at 12 Months Post Transplantation	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.	approximately Month 13	No

External Links

•   Further information on non-Hodgkin's lymphoma from the National Cancer Institute