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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

Primary Purpose

Multiple Myeloma, Lymphoma, Non-Hodgkin

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
G-CSF Plus Plerixafor
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Non-Hodgkin's Lymphoma, Multiple Myeloma, stem cell mobilization, AMD3100, autologous transplantation

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Tom Baker Cancer Center
  • Vancouver General Hospital, BC Cancer Agency

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Non-Hodgkin's Lymphoma (NHL)

Multiple Myeloma (MM)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)
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').

Secondary Outcome Measures

Number of Participants Who Had a ≥ 2-fold Increase in Circulating CD34+ Cells
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
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
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)
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)
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)
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)
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)
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
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
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).

Full Information

First Posted
November 2, 2006
Last Updated
February 4, 2014
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00396266
Brief Title
AMD3100 (Plerixafor) Given to NHL and MM Patients to Increase the Number of PBSCs When Given a Mobilizing Regimen of G-CSF
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Lymphoma, Non-Hodgkin
Keywords
Non-Hodgkin's Lymphoma, Multiple Myeloma, stem cell mobilization, AMD3100, autologous transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Non-Hodgkin's Lymphoma (NHL)
Arm Type
Experimental
Arm Description
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.
Arm Title
Multiple Myeloma (MM)
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
G-CSF Plus Plerixafor
Other Intervention Name(s)
Mozobil, AMD3100
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)
Description
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').
Time Frame
Day 1 to approximately Day 38 (before start of chemotherapy)
Secondary Outcome Measure Information:
Title
Number of Participants Who Had a ≥ 2-fold Increase in Circulating CD34+ Cells
Description
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.
Time Frame
Time 0 to 11 hours after the first dose of plerixafor
Title
Number of Transplants Resulting In Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post-Transplant
Description
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.
Time Frame
2 months
Title
Tumor Cell Mobilization in Non-Hodgkin's Lymphoma (NHL) Participants Following Plerixafor Treatment
Description
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.
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.
Title
Single-dose Maximum Observed Concentration of Plerixafor (Cmax)
Description
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.
Time Frame
Day 5 - 0 to 10 hours post-first plerixafor dose.
Title
Single-dose Time to Maximum Concentration of Plerixafor (Tmax)
Description
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.
Time Frame
Day 5 - 0 to 10 hours post-first plerixafor dose
Title
Single-dose Half-life of Plerixafor (T1/2)
Description
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.
Time Frame
Day 5 - 0 to 10 hours post-first plerixafor dose.
Title
Single-dose Area Under the Concentration-time Curve of Plerixafor From Time 0 to 10 Hours Post-dose (AUC0-10)
Description
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.
Time Frame
Day 5 - 0 to 10 hours post-first plerixafor dose.
Title
Single-dose Apparent Clearance of Plerixafor (CL/F)
Description
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.
Time Frame
Day 5 - 0 to 10 hours post-first plerixafor dose.
Title
Single-dose Apparent Volume of Distribution of Plerixafor (Vz/F) in NHL and MM Patients
Description
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.
Time Frame
Day 5 - 0 to 10 hours post-first plerixafor dose.
Title
Maximum Fold Increase in Peripheral Blood CD34+ Cells From Baseline Following Initial Administration of Plerixafor
Description
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).
Time Frame
Day 4 (10 hours post first plerixafor dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor, MD
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Tom Baker Cancer Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Vancouver General Hospital, BC Cancer Agency
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E3
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
19135941
Citation
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.
Results Reference
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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

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