An Exploratory Safety Study to Investigate the Extent of Tumor Cell Mobilization (TCM) After Use of G-CSF Alone or G-CSF Plus Plerixafor in Multiple Myeloma (MM) Patients Who May be Poor Mobilizers of Stem Cells

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate tumor cell mobilization (TCM) with non-pegylated G-CSF alone compared with non-pegylated G-CSF plus plerixafor in patients with multiple myeloma (MM) who are potentially poor mobilizers of hematopoietic stem cells (HSC). Second objectives are to evaluate survival and disease status of G-CSF alone compared with GCSF plus plerixafor, and the efficacy and safety of G-CSF plus plerixafor when used to mobilize stem cells for autologous transplantation.

Official Title
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A Pilot, Exploratory, Randomized, Phase 2 Safety Study Evaluating Tumor Cell (Plasma Cell) Mobilization and Apheresis Product Contamination in Plerixafor Plus Non-pegylated G-CSF Mobilized Patients and in Non-pegylated G-CSF Alone Mobilized Patients

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Plerixafor
* Drug: Granulocyte-colony stimulating factor (G-CSF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of MM in partial response or complete response, who are undergo an autologous hematopoietic stem cell transplantation and could be considered potentially poor mobilizers. Exclusion Criteria: Does not have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Has a history of any acute or chronic leukemia (including myelodysplastic syndrome). Had prior allogeneic or autologous transplantation. Less than 3 to 6 weeks since last anti-cancer therapy. Chemotherapy for mobilization is not allowed. Has bone marrow involvement >10% assessed based on the most recent bone marrow aspirate or biopsy performed prior to first dose of G-CSF. Was treated with G-CSF or other cytokine within 14 days prior to the first dose of G-CSF for mobilization. Has previously received plerixafor. Is known to be HIV positive. Has active hepatitis B or hepatitis C. Has an acute infection within 24 hours prior to dosing or antibiotic therapy within 7 days prior to the first dose of G-CSF. Has hypercalcaemia as evidenced by >1 mg/dL above upper limit of normal (ULN). Previously received investigational therapy within 4 weeks of screening in this protocol or currently enrolled in another investigational protocol during the mobilization phase. Has central nervous system involvement including brain metastases or leptomeningeal disease. Has an electrocardiogram (ECG) or study result indicative of cardiac ischemia or a history of clinically significant rhythm disturbance(arrhythmias), or other conduction abnormality. Has co-morbid condition(s), which may render the patient at high risk from treatment complications or impairs his/her ability to comply with the study treatment and protocol. Has a white blood cell (WBC) count <2.5 x 10^9/L. Has an absolute neutrophil count (ANC) <1.5 x 10^9/L. Has a platelet count <100 x 10^9/L. Has an estimated creatine clearance ≤50 mL/min. Has aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT), and total bilirubin ≥2.5 x ULN. Does not have adequate cardiac, and pulmonary function sufficient to undergo apheresis and transplantation. Pregnant or breastfeeding women. Does not agree to use a highly effective method of contraception while on study treatment and for at least 3 months following study treatment.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: G-CSF alone<br>Patients will receive G-CSF for 5 consecutive days | Drug: Granulocyte-colony stimulating factor (G-CSF)<br>* 10 mcg/kg, solution, subcutaneous injection<br>|
| Experimental: G-CSF plus plerixafor<br>Patients will receive G-CSF for 4 consecutive days, then receive plerixafor before the 5th dose of G-CSF | Drug: Plerixafor<br>* 240mcg/kg, solution, subcutaneous injection<br>* Other names: Mozobil,AMD3100;Drug: Granulocyte-colony stimulating factor (G-CSF)<br>* 10 mcg/kg, solution, subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The presence of myeloma tumor cells as measured by the percentage of myeloma tumor cells/CD34+ cells | Peripheral blood parameters | Day 1 to Day 8 of the apheresis/treatment period | 
| The presence of myeloma tumor cells as measured by the percentage of myeloma tumor cells/plerixafor cumulative dose/kg body weights | Peripheral blood parameters | Day 5 to Day 8 of the apheresis/treatment period | 
| The presence of myeloma tumor cells as measured by the percentage of myeloma tumor cells/G-CSF cumulative dose/kg body weight | Peripheral blood parameters | Day 5 to Day 8 of the apheresis/treatment period | 
| The change in tumor cell mobilization(TCM) in the peripheral blood | Peripheral blood parameters | Day 4 pre-G-CSF to Day 5 pre-G-CSF | 
| The number of myeloma tumor cells per patient at each apheresis | Apheresis product parameters | Day 1 to Day 8 of the apheresis/treatment period | 
| The number of patients who mobilize at least 4.5x10^5 myeloma tumor cells/kg body weight as measured in each apheresis product | Apheresis product parameters | Day 5 to Day 8 of the apheresis/treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD34+ stem cell yield in the apheresis product |  | Day 1 to Day 8 of the apheresis/treatment period | 
| The number of patients that proceed to transplantation |  | Up to 2 months after final apheresis | 
| Overall survival |  | Day 100 post transplant and up to 2 years post first-G-CSF dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic stem cell transplantation, Tumour cell mobilization