Evaluation of Plerixafor Plus G-CSF to Mobilize and Collect 5×10^6CD34+ Cells/kg in Non-Hodgkin's Lymphoma (NHL) Patients for Autologous Transplantation

Study Overview
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Brief Summary
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The study is to determine if NHL patients mobilized with G-CSF (10 µg/kg/day [GRAN® only]) plus 0.24 mg/kg/day of plerixafor are more likely to achieve a target number of ≥5 × 10^6 CD34+ cells/kg in 4 or fewer days of apheresis than NHL patients mobilized with G-CSF plus placebo.

Detailed Description
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Eligible patients who are unable to achieve adequate apheresis cell counts may enter an Open-Label Rescue Period where they will receive plerixafor, following the same study schedule as during the Double-Blind Treatment Period.

Official Title
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A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative Trial of Plerixafor (0.24 mg/kg) Plus G CSF (10 µg/kg) Versus G CSF (10 µg/kg) Plus Placebo to Mobilize and Collect ≥5 × 106 CD34+ Cells/kg in Non-Hodgkin's Lymphoma (NHL) Patients for Autologous Transplantation

Conditions
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Non-Hodgkin's Lymphoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a biopsy-confirmed diagnosis of NHL Is in first or second complete remission or partial remission, defined for the purpose of this study as complete or partial response following first- or second-line therapy Treatment with an autologous peripheral HSC transplant is planned and the patient is eligible for autologous transplantation Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Has recovered from all acute toxic effects of prior chemotherapy or other cancer treatment. Has an actual body weight <175% of their ideal body weight (IBW) The patient agrees to use a highly effective method of contraception from Day 1 through ≥3 months following plerixafor treatment. Exclusion Criteria: Concurrent serious illness and pathological conditions Has undergone previous HSC collections or collection attempt Has had any autologous or allogeneic HSC transplant Has active central nervous system (CNS) involvement Bone marrow lymphoma cells involvement >20%, as assessed by bone marrow biopsy within 4 months before signing the ICF Has received radiation therapy to the pelvis Has a diagnosis of all leukemias including any type of CLL Active infection Pregnant or nursing Anticipated post-transplant chemotherapy and/or radiation therapy below the diaphragm Received any prior radio-immunotherapy Prior 1,3-bis(2-chloroethyl)-1-nitroso-urea (BCNU) within 6 weeks prior to first dose of G-CSF Prior cancer therapy, other investigational therapy within 4 weeks prior to first dose of G-CSF Prior granulocyte/macrophage-colony stimulating factor (GM-CSF) or pegfilgrastim within 3 weeks prior to the first dose of G-CSF Prior G-CSF within 2 weeks prior to the first dose of G-CSF Inadequate organ funtion evidenced by unacceptable laboratory result

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 + plerixafor<br>Patients will receive G-CSF for 4 mornings for mobilization, followed by another dose each morning before apheresis on days that the patient is to continue apheresis (up to 8 doses total). Patients will also receive plerixafor in the evening up to a maximum of 4 doses. | Drug: Granulocyte-colony stimulating factor (G-CSF)<br>* 10 µg/kg/day G-CSF, administered by subcutaneous (SC) injection<br>* Other names: GRAN®, Filgrastim;Drug: Plerixafor<br>* 0.24 mg/kg/day subcutaneous injection<br>* Other names: Mozobil, AMD3100, GZ316455;|
| Placebo Comparator: G-CSF + Placebo<br>Patients will receive G-CSF for 4 mornings for mobilization, followed by another dose each morning before apheresis on days that the patient is to continue apheresis (up to 8 doses total). Patients will also receive placebo in the evening up to a maximum of 4 doses. | Drug: Granulocyte-colony stimulating factor (G-CSF)<br>* 10 µg/kg/day G-CSF, administered by subcutaneous (SC) injection<br>* Other names: GRAN®, Filgrastim;Drug: Placebo<br>* 0.24mg/kg/day placebo (0.9% Sodium Chloride) administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who meet the target of ≥5 × 10^6 CD34+ cells/kg in 4 or fewer days of apheresis |  | Days 5- Day8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who achieve ≥2 × 10^6 CD34+ cells/kg within 4 or fewer days of apheresis |  | Day 5 - Day 8 | 
| Number of days of apheresis to collect ≥2 × 10^6 CD34+ cells/kg |  | Up to achieve the target of collecting ≥2 × 10^6 CD34+ cells/kg | 
| Number of days of apheresis to collect ≥5 × 10^6 CD34+ cells/kg |  | Up to achieve the target of collecting ≥5 × 10^6 CD34+ cells/kg | 
| Total number of CD34+ cells collected |  | Day 5 - Day 8 | 
| Time from transplantation to neutrophil and platelet (PLT) engraftment |  | up to 30 days post-transplantation | 
| Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) |  | from signed Informed Consent Form (ICF) to 30 days post-transplant and then ongoing as needed | 
| Maximum plasma concentration (Cmax) |  | Day 4 - Day 5 | 
| Time to reach Cmax (Tmax) |  | Day 4 - Day 5 | 
| Area Under the Curve 0 to 10 hours post-dose (AUC0-10) |  | Day 4 - Day 5 | 
| Area Under the Curve 0 to last observed concentration (AUClast) |  | Day 4 - Day 5 | 
| Area Under the Curve (AUC) |  | Day 4 - Day 5 | 
| Percentage of extrapolation of AUC (AUCext) |  | Day 4 - Day 5 | 
| Half life (T1/2) |  | Day 4 - Day 5 | 
| Volume of distribution (Vz/F) |  | Day 4 - Day 5 | 
| Total body clearance (CL/F) |  | Day 4 - Day 5 | 
| Peripheral blood CD34+ cell counts (Pharmacodynamic analysis) |  | Day 4 - Day 5 | 
| The fold-increase in the number of circulating CD34+ following the first dose of plerixafor or placebo, with the first apheresis day (Day 5) value serving as the primary estimate |  | Day 5 - Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation