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

• ClinicalTrials.gov Identifier: NCT01164475
• Recruitment Status: Completed
• First Posted: July 16, 2010
• Results First Posted: January 31, 2014
• Last Update Posted: February 25, 2014
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Description

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: October 2010
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: February 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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.
2. 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 ]

Secondary Outcome Measures :

1. 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 ]
   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.
2. Median Number of Days of Apheresis to Collect at Least 2*10^6 CD34+ Cells/kg [ Time Frame: Day 5 up to Day 8 ]
3. Median Number of Days of Apheresis to Collect at Least 5*10^6 CD34+ Cells/kg [ Time Frame: Day 5 up to Day 8 ]
4. Total Number of CD34+ Cells/kg Collected Over up to 4 Aphereses [ Time Frame: 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.
5. 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) ]
   Fold increase was calculated as CD34+ cell count on Day 5 divided by CD34+ cell count on Day 4.
6. 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 ]
7. 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 ]
8. 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 ]
   T1/2 is the time required for the plasma concentration to decrease to one half.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 78 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01164475
• Other Study ID Numbers: MOZ11809; MSC12830 ( Other Identifier: Other Company study code )
• First Posted: July 16, 2010
• Results First Posted: January 31, 2014
• Last Update Posted: February 25, 2014
• Last Verified: February 2014

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Plerixafor; Lenograstim; Sargramostim; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents