Mobilization of Stem Cells With AMD3100 (Plerixafor) in Multiple Myeloma Patients

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00103662
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, generic name of filgrastim) is better than G-CSF alone to mobilize and collect the optimal number of stem cells in multiple myeloma patients for autologous transplantation.


Condition Intervention Phase
Multiple Myeloma
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: 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 ≥ 6*10^6 CD34+ Cells/kg in Multiple Myeloma Patients for Autologous Transplantation

Resource links provided by NLM:


Further study details as provided by Sanofi:

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

  • Proportion of Participants Achieving a Target of ≥ 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 to ≥6*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 have experienced the event, accounting for censored values) in each treatment arm to collect an optimum number of cells (≥6*10^6 CD34+ cells/kg) for transplantation.

  • 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 and was evaluated up to 12 months post transplant.

  • 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 and was evaluated up to 12 months post transplant.

  • 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 at 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: 302
Study Start Date: January 2005
Study Completion Date: January 2008
Primary Completion Date: October 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 ≥ 6*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:
  • Mozobil
  • AMD3100
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 ≥ 6*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 (G-CSF)is better than filgrastim (G-CSF) alone in helping multiple myeloma patients collect at least 6 million stem cells in two 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:

  • Diagnosis of multiple myeloma in first or second complete or partial remission
  • >= 4 weeks since last cycle of chemotherapy (thalidomide, dexamethasone, and Velcade were not considered prior chemotherapy for the purpose of this study)
  • Recovered from all acute toxic effects of prior chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • White Blood Cell count (WBC) > 2.5*10^9/L
  • Absolute polymorphonuclear leukocytes (PMN) count > 1.5*10^9/L
  • Platelet (PLT) > 100*10^9/L
  • Serum creatinine <=2.2 mg/dL
  • Cardiac and pulmonary status sufficient to undergo apheresis and transplantation
  • Negative for HIV

Exclusion Criteria):

  • Failed previous stem cell collection
  • Previous stem cell transplantation
  • Brain metastases or myelomatous meningitis
  • Radiation to ≥ 50% of the pelvis
  • Abnormal electrocardiogram (ECG) with rhythm disturbance (ventricular arrhythmias) or other conduction abnormality
  • Received bone-seeking radionuclides (e.g. holmium)
  • A residual acute medical condition resulting from prior chemotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00103662

  Show 39 Study Locations
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
ClinicalTrials.gov Identifier: NCT00103662     History of Changes
Obsolete Identifiers: NCT00248417
Other Study ID Numbers: AMD3100-3102, 2005-003599-39
Study First Received: February 11, 2005
Results First Received: February 2, 2009
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Bundesinstitut Arzneimittel und medizinprodukte (BfArM)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenograstim
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014