Back to resultsTreatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients
Primary Purpose
Lymphoma, Non-Hodgkin, Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
G-CSF Plus Plerixafor
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Non-Hodgkin's lymphoma, Multiple Myeloma, Stem cell mobilization
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 Negative for human immunodeficiency virus (HIV) Women of child bearing potential who 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 History of paresthesias 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 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
- University of Cologne
- Carl Gustav Carus University Hospital
- University of Heidelberg
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 (approximately day 38). 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 step scale from 'not related' to 'definitely related').
Secondary Outcome Measures
Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL After First Dose of Plerixafor
The fold increase was measured using local lab values and is the ratio of post first dose (pre-apheresis) PB CD34+ cells/µL)/pre-plerixafor dosing PB CD34+ cells/µL)
Number of Transplants in Which Participants Achieved Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) 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.
Increase in Peripheral Blood (PB) CD34+ Cells From Steady-state Hematopoiesis to Pre-leukapheresis in G-CSF+Plerixafor Treated Participants Compared to Historical Controls Treated With G-CSF Alone or Chemotherapy and G-CSF
A comparison of the effectiveness in mobilizing peripheral blood CD34+ cells between this study's treatment regimen (G-CSF plus plerixafor) to other treatment options: G-CSF alone, and chemotherapy with G-CSF.
Full Information
NCT ID
NCT00322842
First Posted
May 4, 2006
Last Updated
February 10, 2014
Sponsor
Genzyme, a Sanofi Company
Collaborators
AnorMED
1. Study Identification
Unique Protocol Identification Number
NCT00322842
Brief Title
Treatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients
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
September 2004 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
February 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Genzyme, a Sanofi Company
Collaborators
AnorMED
4. Oversight
5. Study Description
Brief Summary
This study evaluates the safety of plerixafor and other outcomes that are purely exploratory in nature. One other pre-specified outcome is to evaluate an interval of 10-11 hours between dosing with plerixafor and the beginning of apheresis to determine if there will be at least a 2-fold increase in circulating CD34+ cells. Data from this protocol will assist in the determination of the dosing schedule for future studies.
Detailed Description
Participants with non-Hodgkin's lymphoma and multiple myeloma who have undergone prior cyto-reductive chemotherapy and are to be autologously transplanted will be treated with a combination of plerixafor and granulocyte colony-stimulating factor (G-CSF) mobilization regimen on the day prior to apheresis. The only change to standard of European care is the addition of plerixafor to a G-CSF mobilizing regimen. Participants will undergo mobilization with G-CSF (10 µg/kg each day) and on each day prior to apheresis will receive plerixafor (240 µg/kg). Participants will undergo apheresis for up to 5 consecutive days in order to collect the target number of (≥ 5*10^6) CD34+ stem cells/kg. Participants will be transplanted with cells obtained from the G-CSF and plerixafor mobilization regimen. The number of CD34+ cells mobilized in the peripheral blood from the time of the plerixafor dose to just prior to apheresis and those harvested in the apheresis product will be measured. The number of apheresis sessions required to obtain ≥ 5*10^6 CD34+ cells/kg will also be measured. Success of the transplantation(s) will be evaluated by the time to engraftment of poly-morphonuclear leukocytes (PMN) and platelets (PLT). Participants will be followed for durability of their transplant for 12 months following transplantation.
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
Lymphoma, Non-Hodgkin, Multiple Myeloma
Keywords
Non-Hodgkin's lymphoma, Multiple Myeloma, Stem cell mobilization
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (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 (approximately day 38). 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 step scale from 'not related' to 'definitely related').
Time Frame
Day 1 to approximately Day 38 (before start of chemotherapy)
Secondary Outcome Measure Information:
Title
Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL After First Dose of Plerixafor
Description
The fold increase was measured using local lab values and is the ratio of post first dose (pre-apheresis) PB CD34+ cells/µL)/pre-plerixafor dosing PB CD34+ cells/µL)
Time Frame
Days 4-5 (first dose of plerixafor to apheresis)
Title
Number of Transplants in Which Participants Achieved Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) 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
Increase in Peripheral Blood (PB) CD34+ Cells From Steady-state Hematopoiesis to Pre-leukapheresis in G-CSF+Plerixafor Treated Participants Compared to Historical Controls Treated With G-CSF Alone or Chemotherapy and G-CSF
Description
A comparison of the effectiveness in mobilizing peripheral blood CD34+ cells between this study's treatment regimen (G-CSF plus plerixafor) to other treatment options: G-CSF alone, and chemotherapy with G-CSF.
Time Frame
up to day 8
Other Pre-specified Outcome Measures:
Title
Median Cumulative Number of CD34+ Cells Collected During Apheresis
Description
Median total number of CD34+ cells collected during apheresis as measured by a central lab.
Time Frame
Days 5-8
Title
Number of Transplants in Which Participants Achieved Platelet (PLT) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant
Description
Participants were monitored for platelet (PLT) 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
Number of Participants With Durable Engraftment 12 Months After Transplantation
Description
The number of participants maintaining a durable graft 12 months after autologous transplantation. A durable graft is defined as the maintenance of normal blood counts.
Time Frame
Approximately 13 months (12 months post-transplant )
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
Negative for human immunodeficiency virus (HIV)
Women of child bearing potential who 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
History of paresthesias
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
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
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
University of Cologne
City
Cologne
Country
Germany
Facility Name
Carl Gustav Carus University Hospital
City
Dresden
Country
Germany
Facility Name
University of Heidelberg
City
Heidelberg
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
16863911
Citation
Fruehauf S, Seeger T, Maier P, Li L, Weinhardt S, Laufs S, Wagner W, Eckstein V, Bridger G, Calandra G, Wenz F, Zeller WJ, Goldschmidt H, Ho AD. The CXCR4 antagonist AMD3100 releases a subset of G-CSF-primed peripheral blood progenitor cells with specific gene expression characteristics. Exp Hematol. 2006 Aug;34(8):1052-9. doi: 10.1016/j.exphem.2006.06.003.
Results Reference
background
PubMed Identifier
19597422
Citation
Fruehauf S, Ehninger G, Hubel K, Topaly J, Goldschmidt H, Ho AD, Muller S, Moos M, Badel K, Calandra G. Mobilization of peripheral blood stem cells for autologous transplant in non-Hodgkin's lymphoma and multiple myeloma patients by plerixafor and G-CSF and detection of tumor cell mobilization by PCR in multiple myeloma patients. Bone Marrow Transplant. 2010 Feb;45(2):269-75. doi: 10.1038/bmt.2009.142. Epub 2009 Jul 13.
Results Reference
result
PubMed Identifier
19929463
Citation
Fruehauf S, Veldwijk MR, Seeger T, Schubert M, Laufs S, Topaly J, Wuchter P, Dillmann F, Eckstein V, Wenz F, Goldschmidt H, Ho AD, Calandra G. A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Cytotherapy. 2009;11(8):992-1001. doi: 10.3109/14653240903121245.
Results Reference
result
Learn more about this trial
Treatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients
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