Clinical trial NCT01164475: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-07-16
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Patients Who Achieved at Least 5*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg)
timeFrame: Day 5 up to Day 8
measure: Area Under the Concentration-time Curve From Time 0 to 10 Hours (AUC [0-10])
timeFrame: 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 outcomes:
measure: Proportion of Patients Who Achieved at Least 2*10^6 CD34+ Cells/kg in Less Than or Equal to 4 Days of Apheresis
timeFrame: Day 5 up to Day 8
measure: Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg
timeFrame: Day 5 up to Day 8
measure: Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg
timeFrame: Day 5 up to Day 8
measure: Total Number of CD34+ Cells/kg Collected Over up to 4 Aphereses
timeFrame: Day 5 up to Day 8
measure: Mean Fold Increase in Peripheral Blood CD34+ Cell Count Following Plerixafor
timeFrame: Baseline (pre G-CSF dose on Day 4) to Day 5 (prior to first apheresis)
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Time to Reach Maximum Plasma Concentration (Tmax)
timeFrame: 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
measure: Terminal Elimination Half-life (T1/2)
timeFrame: 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
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: