Mobilization of Stem Cells With Plerixafor, Chemotherapy and G-CSF in Multiple Myeloma or Non-Hodgkin's Lymphoma Patients

Study Overview
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Brief Summary
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Patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) will be mobilized with chemotherapy and G-CSF plus plerixafor (AMD3100). The purpose of this protocol is to determine if plerixafor given after chemotherapy and G-CSF mobilization regimen is safe, if it can increase the circulating levels of peripheral blood stem cells (PBSCs) by ≥ 2-fold before apheresis, and if transplantation with the apheresis product was successful, as measured by time to engraftment of polymorphonuclear leukocytes (PMNs) and platelets (PLTs).

Detailed Description
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An open label, multi-center, phase 2 study was conducted in patients with MM or NHL who were to be treated with peripheral blood stem cells (PBSC) autologous transplantation. The only change to the standard of care was the addition of plerixafor to a mobilization regimen of chemotherapy and G-CSF. Patients were first given a mobilizing regimen of chemotherapy as per local practice guidelines and G-CSF (at customary doses) and apheresis was performed. After the first apheresis, plerixafor was given at 10PM, 10-11 hours before the second apheresis the next day or in the morning of the second day, 6 hours before the second apheresis. The change in the patient's peripheral CD34+ cell count between the plerixafor dose and the start of apheresis was measured. The apheresis yields on Day 1 and Day 2 were compared. 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.

Official Title
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Treatment With Plerixafor in Multiple Myeloma or Non-Hodgkin's Lymphoma Patients to Increase the Number of Peripheral Blood Stem Cells When Given With A Mobilizing Regimen of Chemotherapy and G-CSF

Conditions
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Lymphoma, Non-Hodgkin, Multiple Myeloma

Intervention / Treatment
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* Drug: G-CSF and plerixafor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Abbreviated List): MM in first partial response/complete response, first relapse, or second partial/complete response NHL in first or second partial or complete remission NHL patients who do not have bone marrow involvement and < 10% for follicular involvement MM patients who have stable disease with < 40% bone marrow involvement No more than three prior regimens of chemotherapy (thalidomide and Decadron are not considered chemotherapy) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 White blood cell count (WBC) >3.0 x 10^9/L Absolute neutrophil count >1.5 x 10^9/L Platelet count >100 x 10^9/L Exclusion Criteria (Abbreviated List): Brain metastases or carcinomatous meningitis Hypercalcaemia [>1 mg/dl above the upper limit of normal (ULN)] Cardiovascular disease that includes proven or predisposition to ventricular arrhythmias Acute Infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plerixafor PM<br>Participants received chemotherapy and G-CSF mobilization for 7 days according to standard procedures at the study center. When participants achieved a target CD34+ count of ≥20 cells/µL, apheresis began. G-CSF was given daily in the morning on the days of apheresis. After the first apheresis, plerixafor (240 µg/kg) was administered each evening (approximately 10pm) followed by apheresis 10 to 11 hours later for up to 4 consecutive days. Called 'Cohort A' in protocol, study report and publications. | Drug: G-CSF and plerixafor<br>* G-CSF and plerixafor were administered as described in the treatment arms.<br>* Other names: AMD3100;|
| Experimental: Plerixafor AM<br>Participants received chemotherapy and G-CSF mobilization for 7 days according to standard procedures at the study center. When participants achieved a target CD34+ count of ≥20 cells/µL, apheresis began. G-CSF was given daily in the morning on the days of apheresis. The morning of the second day after the first apheresis, plerixafor (240 µg/kg) was administered followed by apheresis 6 hours later. Plerixafor (240 µg/kg) was administered in the morning followed by apheresis 6 hours later for up to 4 consecutive days. Called 'Cohort B' in protocol, study report and publications. | Drug: G-CSF and plerixafor<br>* G-CSF and plerixafor were administered as described in the treatment arms.<br>* Other names: AMD3100;|
| Experimental: Low CD34+ Count/ Plerixafor PM<br>Participants received chemotherapy and G-CSF mobilization for 7 days according to standard procedures at the study center. If participants had a CD34+ count of >=10 cells/µL but <20 cells/µL on 2 consecutive days, plerixafor (240 µg/kg) was given in the evening. G-CSF was administered and apheresis performed in the morning. Plerixafor (240 µg/kg) administered in the evening followed by G-CSF and apheresis 10 to 11 hours later was repeated for up to 4 consecutive days. Called 'Cohort C' in protocol, study report and publications. | Drug: G-CSF and plerixafor<br>* G-CSF and plerixafor were administered as described in the treatment arms.<br>* Other names: AMD3100;|
| Experimental: Plerixafor After Chemo<br>This investigational cohort evaluated the effect of administering plerixafor before white blood cell recovery. Participants received mobilizing chemotherapy, followed by 5 consecutive days of G-CSF (10 µg/kg). Starting on the sixth day, participants received G-CSF (10 µg/kg) plus plerixafor (240 µg/kg) daily for up to 3 consecutive days. If CD34+ counts reached >= 20 cells/µL 6 hours after any of the 3 plerixafor doses, apheresis began. If not, G-CSF administration continued until the participant qualified for one of the other treatment arms. Called 'Investigational Cohort' in protocol, study report and publications. | Drug: G-CSF and plerixafor<br>* G-CSF and plerixafor were administered as described in the treatment arms.<br>* Other names: AMD3100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Participant Counts of Adverse Events (AEs) Up to Twelve Months Post Transplant | Safety assessment was based on the incidence of adverse event reports. Participant count of AEs (Adverse Events) by severity and by relationship to study drug. AEs were reported regardless of relationship to study treatment. The investigator graded each AE using the World Health Organization (WHO) Adverse Event Grading Scale and provided assessments of seriousness and relatedness to study treatment. | 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL | The fold increase was measured by fluorescence activated cell sorting (FACS) analysis and was expressed as a ratio. Fold increase = (pre-apheresis PB CD34+ cells/µL)/(pre-plerixafor dosing PB CD34+ cells/µL). | Days 4-5 (first dose of plerixafor to apheresis) | 
| 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. | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin's Lymphoma, Multiple Myeloma, Stem cell mobilization