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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Granulocyte colony-stimulating factor plus plerixafor
* Drug: Granulocyte colony-stimulating factor plus placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF plus plerixafor<br> | Drug: Granulocyte colony-stimulating factor plus plerixafor<br>* 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.<br>* Other names: AMD3100;|
| Placebo Comparator: G-CSF plus placebo<br> | Drug: Granulocyte colony-stimulating factor plus placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Achieving a Target of ≥ 6*10^6 CD34+ Cells/kg in 2 or Fewer Days of Apheresis. | 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. | up to Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | 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. | up to Day 38 | 
| Proportion of Participants Achieving a Target of ≥ 6*10^6 CD34+ Cells/kg in 4 or Fewer Days of Apheresis. | 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. | up to Day 8 | 
| Proportion of Participants Achieving a Target of ≥ 2*10^6 CD34+ Cells/kg in 4 or Fewer Days of Apheresis. | 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. | up to Day 8 | 
| Median Number of Days to ≥6*10^6 CD34+ Cells/kg | 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. | up to Day 8 | 
| Median Number of Days to Polymorphonuclear (PMN) Cell Engraftment | 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. | Up to Month 13 | 
| Median Number of Days to Platelet (PLT) Engraftment | 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. | Up to Month 13 | 
| Graft Durability at 100 Days Post Transplantation | 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. | approximately Day 138 | 
| Graft Durability at 6 Months Post Transplantation | 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. | approximately Month 7 | 
| Graft Durability at 12 Months Post Transplantation | 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. | approximately Month 13 |