Non-Hodgkin's Lymphoma
Conditions
Brief summary
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.
Interventions
DRUGFixed Dose Plerixafor
DRUGWeight-Based Plerixafor
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Achieved at Least 5*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) | Day 5 up to Day 8 | 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 5 up to Day 8 | The cumulative number of CD34+ cells/kg (body weight) collected over all apheresis sessions (up to a maximum of 4 sessions) was reported. |
| Mean Fold Increase in Peripheral Blood CD34+ Cell Count Following Plerixafor | Baseline (pre G-CSF dose on Day 4) to Day 5 (prior to first apheresis) | Fold increase was calculated as CD34+ cell count on Day 5 divided by CD34+ cell count on Day 4. |
| Proportion of Patients Who Achieved at Least 2*10^6 CD34+ Cells/kg in Less Than or Equal to 4 Days of Apheresis | Day 5 up to Day 8 | 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. |
| 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) | 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 | T1/2 is the time required for the plasma concentration to decrease to one half. |
| 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 | — |
| Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg | Day 5 up to Day 8 | — |
Countries
Canada, South Korea, Taiwan, United States
Participant flow
Recruitment details
The study was conducted at 7 centers in 4 countries between October 13, 2010 and February 26, 2013.
Pre-assignment details
A total of 71 patients were screened of which 10 patients were screen failures. A total of 61 patients were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Fixed Dose Plerixafor 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 (\>=5\*10\^6 cells/kg) was collected or until a maximum 4 apheresis sessions occurred. | 30 |
| Weight-Based Plerixafor 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. | 31 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Progressive disease | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Fixed Dose Plerixafor | Weight-Based Plerixafor | Total |
|---|---|---|---|
| Age, Continuous | 46.13 years STANDARD_DEVIATION 13.4 | 47.84 years STANDARD_DEVIATION 13.59 | 47.00 years STANDARD_DEVIATION 13.41 |
| Number of Patients With Peripheral-Blood (PB) Cluster of Differentiation 34+ (CD34+) Cell Count Greater than or equal to 10 cells/mcL | 10 participants | 10 participants | 20 participants |
| Number of Patients With Peripheral-Blood (PB) Cluster of Differentiation 34+ (CD34+) Cell Count Less than 10 cells per microliter (mcL) | 20 participants | 21 participants | 41 participants |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 29 participants | 29 participants | 58 participants |
| Race/Ethnicity, Customized Race: Asian | 28 participants | 28 participants | 56 participants |
| Race/Ethnicity, Customized Race: White | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 35 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 30 | 25 / 31 |
| serious Total, serious adverse events | 0 / 30 | 3 / 31 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 to 10 Hours (AUC [0-10])
Time frame: 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
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fixed Dose Plerixafor | Area Under the Concentration-time Curve From Time 0 to 10 Hours (AUC [0-10]) | 3991.2 nanogram*hour per milliliter (ng*hr/mL) | Standard Error 1.03 |
| Weight-Based Plerixafor | Area Under the Concentration-time Curve From Time 0 to 10 Hours (AUC [0-10]) | 2792.7 nanogram*hour per milliliter (ng*hr/mL) | Standard Error 1.03 |
Primary
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.
Time frame: Day 5 up to Day 8
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fixed Dose Plerixafor | Proportion of Patients Who Achieved at Least 5*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) | 60.0 percentage of participants |
| Weight-Based Plerixafor | Proportion of Patients Who Achieved at Least 5*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) | 54.8 percentage of participants |
Comparison: The comparison was done using the logistic regression model, adjusted for country and baseline PB CD34+ cell count.p-value: 0.39595% CI: [0.44, 9.17]Regression, Logistic
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 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
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fixed Dose Plerixafor | Maximum Observed Plasma Concentration (Cmax) | 957 ng/mL | Standard Deviation 216 |
| Weight-Based Plerixafor | Maximum Observed Plasma Concentration (Cmax) | 711 ng/mL | Standard Deviation 136 |
Secondary
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.
Time frame: Baseline (pre G-CSF dose on Day 4) to Day 5 (prior to first apheresis)
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fixed Dose Plerixafor | Mean Fold Increase in Peripheral Blood CD34+ Cell Count Following Plerixafor | 5.43 fold increase | Standard Deviation 4.02 |
| Weight-Based Plerixafor | Mean Fold Increase in Peripheral Blood CD34+ Cell Count Following Plerixafor | 5.09 fold increase | Standard Deviation 2.81 |
Secondary
Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg
Time frame: Day 5 up to Day 8
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor. Here, number of patients analyzed = the number of patients who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fixed Dose Plerixafor | Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg | 1 days |
| Weight-Based Plerixafor | Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg | 2 days |
Secondary
Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg
Time frame: Day 5 up to Day 8
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor. Here, number of patients analyzed = the number of patients who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fixed Dose Plerixafor | Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg | 3 days |
| Weight-Based Plerixafor | Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg | 3 days |
Secondary
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.
Time frame: Day 5 up to Day 8
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fixed Dose Plerixafor | Proportion of Patients Who Achieved at Least 2*10^6 CD34+ Cells/kg in Less Than or Equal to 4 Days of Apheresis | 93.3 percentage of participants |
| Weight-Based Plerixafor | Proportion of Patients Who Achieved at Least 2*10^6 CD34+ Cells/kg in Less Than or Equal to 4 Days of Apheresis | 90.3 percentage of participants |
Secondary
Terminal Elimination Half-life (T1/2)
T1/2 is the time required for the plasma concentration to decrease to one half.
Time frame: 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
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fixed Dose Plerixafor | Terminal Elimination Half-life (T1/2) | 4.53 hours | Standard Deviation 1.38 |
| Weight-Based Plerixafor | Terminal Elimination Half-life (T1/2) | 4.27 hours | Standard Deviation 0.93 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: 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
Population: FAS included all patients who have signed informed consent and received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fixed Dose Plerixafor | Time to Reach Maximum Plasma Concentration (Tmax) | 0.50 hours |
| Weight-Based Plerixafor | Time to Reach Maximum Plasma Concentration (Tmax) | 0.50 hours |
Secondary
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.
Time frame: Day 5 up to Day 8
Population: FAS included all randomized patients who signed informed consent form and received at least one dose of plerixafor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fixed Dose Plerixafor | Total Number of CD34+ Cells/kg Collected Over up to 4 Aphereses | 5.35 10^6 cells/kg |
| Weight-Based Plerixafor | Total Number of CD34+ Cells/kg Collected Over up to 4 Aphereses | 5.24 10^6 cells/kg |