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

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01164475
• Other study ID #: MOZ11809
• Secondary ID: MSC12830
• Status: Completed
• Phase: Phase 4
• First received: July 9, 2010
• Last updated: February 7, 2014
• Start date: October 2010
• Est. completion date: February 2013

Study information

• Verified date: February 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSouth Korea: Korea Food and Drug Administration (KFDA)Canada: Health CanadaTaiwan: Department of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Granulocyte-colony stimulating factor (G-CSF)

• Fixed Dose Plerixafor

• Weight-Based Plerixafor

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	St. Mary's Hospital	Seoul
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	City of Hope National Medical Center	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 5 up to Day 8	No
Primary	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	No
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.	Day 5 up to Day 8	No
Secondary	Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg		Day 5 up to Day 8	No
Secondary	Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg		Day 5 up to Day 8	No
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.	Day 5 up to Day 8	No
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.	Baseline (pre G-CSF dose on Day 4) to Day 5 (prior to first apheresis)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No