Plerixafor and Filgrastim Following Cyclophosphamide for Stem Cell Mobilization in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: There are different methods of stem cell mobilization, such as using colony-stimulating factors alone or following chemotherapy priming. More recently, the combination of plerixafor and colony-stimulating factors has been shown to enhance stem cell mobilization. This study will assess whether the combination of plerixafor and Granulocyte Colony-Stimulating Factor (G-CSF) is effective following chemotherapy mobilization with cyclophosphamide. PURPOSE: To assess the safety, tolerability, and best dose of intravenous plerixafor following cyclophosphamide priming.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the safety and tolerability of intravenous(IV) PLERIXAFOR when given in combination with cyclophosphamide and G-CSF as a mobilization regimen in patients with Multiple Myeloma. SECONDARY OBJECTIVES: I. To determine if intravenous PLERIXAFOR, given with a cyclophosphamide and G-CSF mobilizing regimen, will allow collection of greater than or equal to 5 x 10^6 CD34+ cells/kg in 2 or less apheresis days. II. To review the timing of intravenous plerixafor administration prior to apheresis and describe our experience. OUTLINE: MOBILIZATION: Patients receive cyclophosphamide intravenously (IV). Patients also receive filgrastim subcutaneously (SC) daily beginning approximately 24 hours later. TREATMENT/APHERESIS: Beginning 10 days after cyclophosphamide, patients receive plerixafor IV over 30 minutes followed by filgrastim SC on each day of apheresis. Following the collection of an adequate number of stem cells, patients undergo high-dose chemotherapy and autologous stem cell rescue. Patients are followed post-autologous stem cell transplant for engraftment. After completion of study treatment, patients are followed periodically.

Official Title
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A Phase I/Pilot Study of Intravenous PLERIXAFOR Following Cyclophosphamide Mobilization in Patients With Multiple Myeloma

Conditions
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Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Intervention / Treatment
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* Drug: plerixafor
* Biological: filgrastim
* Drug: cyclophosphamide
* Procedure: autologous hematopoietic stem cell transplantation
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Criteria Inclusion and exclusion criteria must be re-evaluated prior to dosing with PLERIXAFOR; if the patient does not meet any of these criteria (excluding the hepatic and hematologic criteria) the patient is not eligible to continue unless Genzyme grants a waiver Inclusion Eligible to undergo autologous transplantation Diagnosed with multiple myeloma (MM) ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 The patient has recovered from all acute toxic effects of prior chemotherapy White Blood Count (WBC) > 2.5 x 10^9/L Absolute neutrophil count >1.5 x 10^9/L Platelet count > 100 x 10^9/L Serum creatinine <= 2.5 mg/dl Creatinine clearance >= 50 ml/min (measured or calculated) Serum glutamic oxaloacetic transaminase (SGOT) < 2 x ULN (Upper Limit of Normal) Serum glutamic pyruvic transaminase (SGPT) < 2 x ULN Total bilirubin < 2 x ULN Left ventricle ejection fraction > 45% [by normal ECHO (Echocardiogram) or MUGA (MUltiple Gated Acquisition) scan] FEV1 (forced expiratory volume in 1 second) > 60% of predicted or DLCO (Carbon Monoxide Diffusing Capacity )> 55% of predicted No active infection of hepatitis B or C Negative for HIV Signed informed consent (may be obtained anytime prior to admission for cytoxan) Women of child bearing potential agree to use an approved form of contraception Exclusion A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications A residual acute medical condition resulting from prior chemotherapy Brain metastases or carcinomatous meningitis Acute infection Fever (temp > 38 degrees C/100.4 degrees F) Positive pregnancy test in female patients Lactating females Patients of child-bearing potential unwilling to implement adequate birth control Prior treatment with Plerixafor Prior stem cell transplant, either autologous or allogeneic Prior cyclophosphamide priming Heart rate < 50 at screening Abnormal ECG (electrocardiogram) with a clinically significant rhythm disturbance or conduction abnormality that in the opinion of the investigator warrants exclusion of the subject from the trial Patients with congestive heart failure at screening History of atrial fibrillation Patients who are currently on medication to control cardiac arrhythmias

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>MOBILIZATION: Patients receive cyclophosphamide IV. Patients also receive filgrastim subcutaneously (SC) daily beginning approximately 24 hours later. TREATMENT/APHERESIS: Beginning 10 days after cyclophosphamide, patients receive plerixafor IV over 30 minutes followed by filgrastim SC on each day of apheresis. | Drug: plerixafor<br>* Given IV<br>* Other names: Mozobil;Biological: filgrastim<br>* Given SC<br>* Other names: Recombinant Methionyl Human Granulocyte Colony Stimulating Factor;Drug: cyclophosphamide<br>* Given IV<br>* Other names: Enduxan;Procedure: autologous hematopoietic stem cell transplantation<br>* autologous hematopoietic stem cell transplantation<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the MTD ( maximum tolerated dose) of IV plerixafor when given post cyclophosphamide and GCSF for stem cell priming.Dose limiting toxicity will be defined as any grade 3 or 4 nonhematologic toxicity. |  | 12 to 18 months | 
| Tolerability and safety of PLERIXAFOR | Will be summarized in terms of type, severity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0), date of onset, duration, reversibility, and attribution. | 6 months post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of collecting 5 x 10^6 or more CD34+ cells/kg in 2 or less apheresis days |  | 5 days post apheresis completion | 
| Percentage of plasma cells |  | 5 days post apheresis | 
| Completion of 100 days post-transplant |  | 100 days post-transplant | 
| Overall and disease-free survival |  | 6months and one year post transplant | 
| Time to engraftment |  | 6 months post transplant |