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Trial record 1 of 1 for:    amd3100c201
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AMD3100 (Plerixafor) Given to NHL and MM Patients to Increase the Number of PBSCs When Given a Mobilizing Regimen of G-CSF

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00396266
Recruitment Status : Completed
First Posted : November 6, 2006
Results First Posted : November 25, 2010
Last Update Posted : March 7, 2014
Sponsor:
Information provided by:
Sanofi

Tracking Information
First Submitted Date  ICMJE November 2, 2006
First Posted Date  ICMJE November 6, 2006
Results First Submitted Date  ICMJE October 30, 2010
Results First Posted Date  ICMJE November 25, 2010
Last Update Posted Date March 7, 2014
Study Start Date  ICMJE January 2005
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2010)
Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE) [ Time Frame: Day 1 to approximately Day 38 (before start of chemotherapy) ]
Number of participants with treatment emergent adverse events (TEAEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related').
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2006)
To determine if AMD3100 is generally safe.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2010)
  • Number of Participants Who Had a ≥ 2-fold Increase in Circulating CD34+ Cells [ Time Frame: Time 0 to 11 hours after the first dose of plerixafor ]
    To determine if NHL and MM patients mobilized with G-CSF (10 µg/kg QD) plus plerixafor will have a ≥2-fold increase in circulating CD34+ cells from time 0 to 11 hours after a dose of plerixafor.
  • Number of Transplants Resulting In Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post-Transplant [ Time Frame: 2 months ]
    Participants were monitored for polymorphonuclear leukocyte (PMN) engraftment as per the local standard of care. The target for engraftment was 12 days after PBSC transplant and no transplant taking longer than 21 days for engraftment.
  • Tumor Cell Mobilization in Non-Hodgkin's Lymphoma (NHL) Participants Following Plerixafor Treatment [ Time Frame: Prior to the first (Day 4) and last dose of plerixafor, immediately prior to each apheresis, and 24 hours after the last apheresis. ]
    In a subpopulation of NHL participants, the mobilization of NHL cells was to be evaluated. None of the samples were analyzed due to sample degradation.
  • Single-dose Maximum Observed Concentration of Plerixafor (Cmax) [ Time Frame: Day 5 - 0 to 10 hours post-first plerixafor dose. ]
    Evaluation of Cmax following a single dose of 240 µg/kg plerixafor administered after 4 days of G-CSF mobilization. Cmax was determined from direct observation of the data.
  • Single-dose Time to Maximum Concentration of Plerixafor (Tmax) [ Time Frame: Day 5 - 0 to 10 hours post-first plerixafor dose ]
    Evaluation of Tmax following a single dose of 240 µg/kg plerixafor administered after 4 days of G-CSF mobilization. Tmax was determined from direct observation of the data.
  • Single-dose Half-life of Plerixafor (T1/2) [ Time Frame: Day 5 - 0 to 10 hours post-first plerixafor dose. ]
    Evaluation of T1/2 following a single dose of 240 µg/kg plerixafor administered after 4 days of G-CSF mobilization. T1/2 was determined from non-compartmental analysis.
  • Single-dose Area Under the Concentration-time Curve of Plerixafor From Time 0 to 10 Hours Post-dose (AUC0-10) [ Time Frame: Day 5 - 0 to 10 hours post-first plerixafor dose. ]
    Evaluation of AUC0-10 following a single dose of 240 µg/kg plerixafor administered after 4 days of G-CSF mobilization. AUC0-10 was determined from non-compartmental analysis.
  • Single-dose Apparent Clearance of Plerixafor (CL/F) [ Time Frame: Day 5 - 0 to 10 hours post-first plerixafor dose. ]
    Evaluation of Cl/F following a single dose of 240 µg/kg plerixafor administered after 4 days of G-CSF mobilization. Cl/F was determined from non-compartmental analysis.
  • Single-dose Apparent Volume of Distribution of Plerixafor (Vz/F) in NHL and MM Patients [ Time Frame: Day 5 - 0 to 10 hours post-first plerixafor dose. ]
    Evaluation of Vz/F following a single dose of 240 µg/kg plerixafor administered after 4 days of G-CSF mobilization. Vz/F was determined from non-compartmental analysis.
  • Maximum Fold Increase in Peripheral Blood CD34+ Cells From Baseline Following Initial Administration of Plerixafor [ Time Frame: Day 4 (10 hours post first plerixafor dose) ]
    A pharmacodynamic evaluation to determine the maximum fold increase in peripheral blood CD34+ cells following the initial administration of plerixafor by measuring the fold increase at time points up to 10 hours post plerixafor relative to baseline (immediately prior to plerixafor).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2006)
  • To determine if NHL and MM patients mobilized with G-CSF (10 µg/kg QD) plus AMD3100 will have a ≥2-fold increase in circulating CD34+ cells from time 0 to 11 hours after a dose of AMD3100.
  • To determine if NHL and MM patients who are mobilized with G-CSF (10 µg/kg QD) plus AMD3100 and transplanted with ≥5 x 10e6 cells/kg will engraft PMNs by day 12, but no later than day 21.
  • To determine if NHL tumor cells are mobilized after either G-CSF mobilization or AMD3100 administration.
  • To examine the pharmacokinetics and pharmacodynamics of a single dose of 240 µg/kg AMD3100 administered after 4 days of G-CSF mobilization in NHL and MM patients.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AMD3100 (Plerixafor) Given to NHL and MM Patients to Increase the Number of PBSCs When Given a Mobilizing Regimen of G-CSF
Official Title  ICMJE Treatment With AMD3100 in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients to Increase the Number of Peripheral Blood Stem Cells When Given a Mobilizing Regimen of G-CSF
Brief Summary This study evaluates the safety and efficacy of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Efficacy outcomes include evaluation of fold increase in circulating CD34+ cells from just before the first plerixafor injection to 10-11 hours post plerixafor (just before apheresis) and assessment of successful polymorphonuclear leukocyte (PMN) engraftment after transplantation. Data from this protocol will assist in the determination of the dosing schedule for future studies.
Detailed Description

Participants with NHL and MM who have undergone prior cyto-reductive chemotherapy, are to be autologously transplanted, and meet the inclusion/exclusion criteria are eligible to enter the study. The only change to the standard of care is the addition of plerixafor to a granulocyte colony-stimulating factor (G-CSF) mobilization regimen on the day prior to apheresis. Participants will undergo mobilization with G-CSF (10 mcg/kg each day) and will receive plerixafor (240 mcg/kg) in the evening prior to apheresis. Participants will undergo apheresis for up to 5 consecutive days in order to collect the target number of CD34+ stem cells (≥ 5*10^6 CD34+ cells/kg for either single or tandem transplant). After apheresis, all participants will be treated with high-dose chemotherapy in preparation for transplantation. Participants will be transplanted with cells obtained from the G-CSF and plerixafor mobilization regimen. The increase in CD34+ cells in the peripheral blood from the time of the plerixafor dose to just prior to apheresis and the number of CD34+ cells in the apheresis product will be measured. Success of the transplantation(s) will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN). A subpopulation will have pharmacokinetic and pharmacodynamic analysis done.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Multiple Myeloma
  • Lymphoma, Non-Hodgkin
Intervention  ICMJE Drug: G-CSF Plus Plerixafor
Participants underwent mobilization with G-CSF 10 µg/kg/day for 4 days, administered by subcutaneous injection (SC) injection each morning. On the evening of Day 4, participants received a dose of plerixafor 240 µg/kg, administered by SC injection. On Day 5, participants returned to the clinic and received a morning dose of G-CSF 10 µg/kg and underwent apheresis approximately 10 to 11 hours after the dose of plerixafor (within 60 minutes after administration of G-CSF). Participants continued to receive an evening dose of plerixafor followed the next day by a morning dose of G-CSF and apheresis for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.
Other Names:
  • Mozobil
  • AMD3100
Study Arms  ICMJE
  • Experimental: Non-Hodgkin's Lymphoma (NHL)
    Participants with NHL were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.
    Intervention: Drug: G-CSF Plus Plerixafor
  • Experimental: Multiple Myeloma (MM)
    Participants with MM were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.
    Intervention: Drug: G-CSF Plus Plerixafor
Publications * Stewart DA, Smith C, MacFarland R, Calandra G. Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. Biol Blood Marrow Transplant. 2009 Jan;15(1):39-46. doi: 10.1016/j.bbmt.2008.10.018.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 30, 2010)
22
Original Enrollment  ICMJE
 (submitted: November 2, 2006)
25
Actual Study Completion Date  ICMJE December 2007
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of non-Hodgkin's lymphoma (NHL) or multiple myoloma (MM) eligible for autologous transplantation
  • No more than 3 prior regimens of chemotherapy
  • More than 4 weeks since last cycle of chemotherapy. Patient recovered from all acute toxic effects of prior chemotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • White blood cell (WBC) count >3.0*10^9/L
  • Absolute polymorphonuclear cells (PMN) count >1.5*10^9/L
  • Platelet (PLT) count >100*10^9/L
  • Serum creatinine <=2.2 mg/dL
  • Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and total bilirubin <2 x upper limit of normal (ULN)
  • Left ventricle ejection fraction >45% by normal echocardiogram or multiple-gated acquisition (MUGA) scan
  • Forced expiratory volume of the lung in the first second (FEV1) >60% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO) >45% of predicted
  • Negative for human immunodeficiency virus (HIV) type 1
  • Women of child bearing potential agreed to use an approved form of contraception.

Exclusion Criteria:

  • • Patients who have failed previous collections

    • Brain metastases or carcinomatous meningitis
    • History of ventricular arrhythmias
    • A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications
    • A residual acute medical condition resulting from prior chemotherapy
    • Acute infection
    • Fever (temp >38°C/100.4°F)
    • Patients whose actual body weight exceeds 150% of their ideal body weight
    • History of paresthesias (at least Grade 2)
    • Patients who previously received experimental therapy within 4 weeks of enrolling in this study or who are currently enrolled in another experimental study during the mobilization period
    • Positive pregnancy test in female patients
    • Lactating females
    • Patients of child-bearing potential unwilling to implement adequate birth control.
    • Patients who have deterioration of their clinical status or laboratory parameters between the time of enrolment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00396266
Other Study ID Numbers  ICMJE AMD3100-C201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Medical Monitor, Genzyme
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor, MD Genzyme, a Sanofi Company
PRS Account Sanofi
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP