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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01164475
First received: July 9, 2010
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Granulocyte-colony stimulating factor (G-CSF)
Drug: Fixed Dose Plerixafor
Drug: Weight-Based Plerixafor
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Proportion of Patients Who Achieved at Least 5*10^6 Cluster of Differentiation 34+ (CD34+) Cells Per Kilogram (Cells/kg) [ Time Frame: Day 5 up to Day 8 ] [ Designated as safety issue: No ]
    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]) [ 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of Patients Who Achieved at Least 2*10^6 CD34+ Cells/kg in Less Than or Equal to 4 Days of Apheresis [ Time Frame: Day 5 up to Day 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 5 up to Day 8 ] [ Designated as safety issue: No ]
  • Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg [ Time Frame: Day 5 up to Day 8 ] [ Designated as safety issue: No ]
  • Total Number of CD34+ Cells/kg Collected Over up to 4 Aphereses [ Time Frame: Day 5 up to Day 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (pre G-CSF dose on Day 4) to Day 5 (prior to first apheresis) ] [ Designated as safety issue: No ]
    Fold increase was calculated as CD34+ cell count on Day 5 divided by CD34+ cell count on Day 4.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Terminal Elimination Half-life (T1/2) [ 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 ] [ Designated as safety issue: No ]
    T1/2 is the time required for the plasma concentration to decrease to one half.


Enrollment: 61
Study Start Date: October 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Granulocyte-colony stimulating factor (G-CSF)
Other Name: Filgrastim
Drug: Fixed Dose Plerixafor
Other Names:
  • Mozobil
  • AMD3100
Active Comparator: 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.
Drug: Granulocyte-colony stimulating factor (G-CSF)
Other Name: Filgrastim
Drug: Weight-Based Plerixafor
Other Names:
  • Mozobil
  • AMD3100

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01164475

Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
St. Mary's Hospital
Seoul, Korea, Republic of, 137-701
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 10002
Taipei Veterans General Hospital
Taipei, Taiwan, 10002
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01164475     History of Changes
Other Study ID Numbers: MOZ11809, MSC12830
Study First Received: July 9, 2010
Results First Received: December 12, 2013
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Canada: Health Canada
Taiwan: Department of Health

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
JM 3100
Lenograstim
Adjuvants, Immunologic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014