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

Phase 4

Completed

• Conditions: Non-Hodgkin's Lymphoma
• Interventions: Drug: Granulocyte-colony stimulating factor (G-CSF); Drug: Fixed Dose Plerixafor; Drug: Weight-Based Plerixafor

• Registration Number: NCT01164475
• Lead Sponsor: Genzyme, a Sanofi Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-07-09
• Study First Submitted QC: 2010-07-15
• Study First Posted: 2010-07-16
• Study Start: 2010-10
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Results First Submitted: 2013-12-12
• Results First Submitted QC: 2013-12-12
• Results First Posted: 2014-01-31
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-07
• Last Update Posted: 2014-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fixed Dose Plerixafor	Granulocyte-colony stimulating factor (G-CSF)	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.
Fixed Dose Plerixafor	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 (greater than or equal to \[\>=\] 5\*10\^6 cells/kg) was collected or until a maximum 4 apheresis sessions occurred.
Weight-Based Plerixafor	Granulocyte-colony stimulating factor (G-CSF)	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.
Weight-Based Plerixafor	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.

Primary Outcome Measures

Name	Time	Method
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
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.

Secondary Outcome Measures

Name	Time	Method
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.
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	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.
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)	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.

Trial Locations

Locations (7)

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan