Evaluation of Approved Weight-Based Dose Compared to Fixed Dose of Plerixafor in Patients With Non-Hodgkin's Lymphoma (NHL) Weighing Less Than 70 Kilograms

Study Overview
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Brief Summary
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The purpose of this study was to compare the responses of 2 different doses of plerixafor in patients with Non-Hodgkin's Lymphoma (NHL) who received an autologous stem cell transplant.

Official Title
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A Phase 4, Multicenter, Randomized, Comparator Trial Evaluating the Standard Weight-Based Dose (0.24 mg/kg) Compared to a Fixed Dose (20 mg) of Plerixafor Injection in Combination With G-CSF to Mobilize and Collect ≥5 x 10^6 CD34+ Cells/kg in ≤4 Days and to Evaluate the Difference in Total Systemic Exposure in Patients With Non-Hodgkin's Lymphoma Weighing ≤70 kg

Conditions
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Non-Hodgkin's Lymphoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 78 years (inclusive) Patients diagnosed with NHL who were to receive treatment with an autologous peripheral stem cell transplant for the first time Biopsy-confirmed diagnosis of NHL (chronic lymphocytic leukemia and all variants were excluded) Weight less than or equal to 70 kg 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 only At least 4 weeks since last cycle of chemotherapy and/or other cancer therapy including rituximab Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Recovered from all acute toxic effects of prior chemotherapy Negative for human immunodeficiency virus (HIV), active hepatitis B, and active hepatitis C from assessments performed within 3 months before signing informed consent Signed informed consent form (ICF) White blood cell count (WBC) greater than (>) 2.5*10^9 per liter (L) Absolute neutrophil count (ANC) >1.5*10^9/L Platelet (PLT) count >100*10^9/L Creatinine clearance >=80 milliliter per minute (mL/min) (estimated by Cockcroft-Gault formula or 24 hour urine collection) Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST), serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT), and total bilirubin less than 2.5*upper limit of normal Cardiac and pulmonary status sufficient to undergo apheresis and transplantation All patients agreed to an effective method of contraception while on study treatment and for at least 3 months following plerixafor treatment (including both female patients of child-bearing potential and male patients with partners of child-bearing potential) Exclusion Criteria: A co-morbid condition which, in the view of the Investigator(s), rendered the patient at high risk from treatment complications Failed previous hematopoietic stem cell (HSC) collections or collection attempts Prior autologous or allogeneic transplant Less than 6 weeks off 1,3-bis (2-chloroethyl)-1-nitroso-urea (BCNU) prior to first dose of G-CSF Active central nervous system involvement, active brain metastases, or any history of carcinomatous meningitis (active or inactive) Bone marrow involvement >20 percent (%), as assessed by bone marrow biopsy within 4 months of the first screening assessment, unless a bone marrow biopsy was performed immediately prior to the last chemotherapy and was negative and the patient responded to last chemotherapy achieving a complete or partial remission Received radiation therapy to the pelvis Received granulocyte/macrophage-colony stimulating factor (GM-CSF) or pegfilgrastim within 3 weeks prior to the first dose of granulocyte colony stimulating factor (G-CSF) for mobilization Received G-CSF within 14 days prior to the first dose of G-CSF for mobilization Received prior radio-immunotherapy with ibritumomab tiuxetan or tositumomab iodine Active infection, including unexplained fever (>38.1 degree Celsius / 100.4 Fahrenheit), or antibiotic, antiviral, or antifungal therapy within 7 days prior to the first dose of G-CSF Positive pregnancy test (female patients) Lactating (female patients) Abnormal electrocardiogram (ECG) with clinically significant rhythm disturbance (ventricular arrhythmias) or other conduction abnormality in the last year that, in the opinion of the Investigator(s), warranted exclusion of the patient from the trial Previously received experimental therapy within 4 weeks of enrolling or who were currently enrolled in another experimental protocol during the G CSF and plerixafor treatment period

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Dose Plerixafor<br>10 microgram per kilogram (mcg/kg) granulocyte-colony stimulating factor (G-CSF) subcutaneous (SC) injection once daily in morning from Day 1 through Day 4 (G-CSF mobilization period), followed by 20 milligram (mg) plerixafor SC injection (fixed dose) in evening of Day 4 (10 to 11 hours prior to first apheresis), and then 10 mcg/kg G-CSF SC injection in morning of Day 5 (1 hour prior to first apheresis). Apheresis process and treatment with plerixafor (10 to 11 hours prior to apheresis) and G-CSF (1 hour prior to apheresis) was continued until the target number of cluster of differentiation 34 (CD34+) stem cells (greater than or equal to [>=] 5*10^6 cells/kg) was collected or until a maximum 4 apheresis sessions occurred. | Drug: Granulocyte-colony stimulating factor (G-CSF)<br> <br> * Other names: Filgrastim;Drug: Fixed Dose Plerixafor<br> <br> * Other names: AMD3100;|
| Active Comparator: Weight-Based Plerixafor<br>G-CSF 10 mcg/kg SC injection once daily in morning from Day 1 through Day 4 (G-CSF mobilization period), followed by plerixafor 0.24 milligram per kilogram (mg/kg) SC injection (weight-based dose) in evening of Day 4 (10 to 11 hours before first apheresis), and then G-CSF 10 mcg/kg SC injection in morning of Day 5 (1 hour prior to first apheresis). Apheresis process and treatment with plerixafor (10 to 11 hours prior to apheresis) and G-CSF (1 hour prior to apheresis) was continued until the target number of CD34+ stem cells (>=5*10^6 cells/kg) was collected or until a maximum 4 apheresis sessions occurred. | Drug: Granulocyte-colony stimulating factor (G-CSF)<br> <br> * Other names: Filgrastim;Drug: Weight-Based Plerixafor<br> <br> * Other names: AMD3100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Achieved at Least 5*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) | The cumulative number of CD34+ cells/kg (body weight) collected over all apheresis sessions (up to a maximum of 4 sessions) was used to determine if a patient has achieved the target of >=5*10^6 CD34+ cells/kg (optimum number of CD34+ cells required for transplantation) within 4 days of apheresis. The proportion of patients who achieved the target was reported as percentages for each treatment arm. | Day 5 up to Day 8 | 
| Area Under the Concentration-time Curve From Time 0 to 10 Hours (AUC [0-10]) |  | 0 (pre-plerixafor dose), 0.5, 1, 4 hours post-plerixafor dose on Day 4; 9-10 hours post-plerixafor dose (pre G-CSF dose) on Day 5, 10-11 hours post-plerixafor dose (prior to first apheresis) on Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Achieved at Least 2*10^6 CD34+ Cells/kg in Less Than or Equal to 4 Days of Apheresis | The cumulative number of CD34+ cells/kg (body weight) collected over all apheresis sessions (up to a maximum of 4 sessions) was used to determine if a patient has achieved the target of >= 2*10^6 CD34+ cells/kg (minimum number of CD34+ cells required for transplantation) within 4 days of apheresis. The proportion of patients who achieved the target was reported as percentages for each treatment arm. | Day 5 up to Day 8 | 
| Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg |  | Day 5 up to Day 8 | 
| Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg |  | Day 5 up to Day 8 | 
| Total Number of CD34+ Cells/kg Collected Over up to 4 Aphereses | The cumulative number of CD34+ cells/kg (body weight) collected over all apheresis sessions (up to a maximum of 4 sessions) was reported. | Day 5 up to Day 8 | 
| Mean Fold Increase in Peripheral Blood CD34+ Cell Count Following Plerixafor | Fold increase was calculated as CD34+ cell count on Day 5 divided by CD34+ cell count on Day 4. | Baseline (pre G-CSF dose on Day 4) to Day 5 (prior to first apheresis) | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0 (pre-plerixafor dose), 0.5, 1, 4 hours post-plerixafor dose on Day 4; 9-10 hours post-plerixafor dose (pre G-CSF dose) on Day 5, 10-11 hours post-plerixafor dose (prior to first apheresis) on Day 5 | 
| Time to Reach Maximum Plasma Concentration (Tmax) |  | 0 (pre-plerixafor dose), 0.5, 1, 4 hours post-plerixafor dose on Day 4; 9-10 hours post-plerixafor dose (pre G-CSF dose) on Day 5, 10-11 hours post-plerixafor dose (prior to first apheresis) on Day 5 | 
| Terminal Elimination Half-life (T1/2) | T1/2 is the time required for the plasma concentration to decrease to one half. | 0 (pre-plerixafor dose), 0.5, 1, 4 hours post-plerixafor dose on Day 4; 9-10 hours post-plerixafor dose (pre G-CSF dose) on Day 5, 10-11 hours post-plerixafor dose (prior to first apheresis) on Day 5 |