Evaluation of Plerixafor Plus G-CSF to Mobilize and Collect 5×10^6CD34+ Cells/kg in Non-Hodgkin's Lymphoma (NHL) Patients for Autologous Transplantation

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative Trial of Plerixafor (0.24 mg/kg) Plus G CSF (10 µg/kg) Versus G CSF (10 µg/kg) Plus Placebo to Mobilize and Collect ≥5 × 106 CD34+ Cells/kg in Non-Hodgkin's Lymphoma (NHL) Patients for Autologous Transplantation

The study is to determine if NHL patients mobilized with G-CSF (10 µg/kg/day [GRAN® only]) plus 0.24 mg/kg/day of plerixafor are more likely to achieve a target number of ≥5 × 10^6 CD34+ cells/kg in 4 or fewer days of apheresis than NHL patients mobilized with G-CSF plus placebo.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Granulocyte-colony stimulating factor (G-CSF); Drug: Plerixafor; Drug: Placebo

Detailed Description

Eligible patients who are unable to achieve adequate apheresis cell counts may enter an Open-Label Rescue Period where they will receive plerixafor, following the same study schedule as during the Double-Blind Treatment Period.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Investigational Site Number 156003
  • Beijing, China, 100034
    • Investigational Site Number 156017
  • Beijing, China, 100044
    • Investigational Site Number 156001
  • Beijing, China, 100071
    • Investigational Site Number 156005
  • Beijing, China, 100142
    • Investigational Site Number 156002
  • Chongqing, China, 400037
    • Investigational Site Number 156020
  • Fuzhou, China, 350001
    • Investigational Site Number 156016
  • Guangzhou, China, 510060
    • Investigational Site Number 156021
  • Hangzhou, China, 310003
    • Investigational Site Number 156011
  • Nanjing, China, 210029
    • Investigational Site Number 156018
  • Shanghai, China, 200025
    • Investigational Site Number 156009
  • Suzhou, China, 215006
    • Investigational Site Number 156010
  • Tianjin, China, 300020
    • Investigational Site Number 156008
  • Wuhan, China, 430022
    • Investigational Site Number 156013
  • Xi'An, China, 710038
    • Investigational Site Number 156015
  • Zhengzhou, China, 450008
    • Investigational Site Number 156022

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has a biopsy-confirmed diagnosis of NHL
• Is 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
• Treatment with an autologous peripheral HSC transplant is planned and the patient is eligible for autologous transplantation
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Has recovered from all acute toxic effects of prior chemotherapy or other cancer treatment.
• Has an actual body weight <175% of their ideal body weight (IBW)
• The patient agrees to use a highly effective method of contraception from Day 1 through ≥3 months following plerixafor treatment.

Exclusion Criteria:

• Concurrent serious illness and pathological conditions
• Has undergone previous HSC collections or collection attempt
• Has had any autologous or allogeneic HSC transplant
• Has active central nervous system (CNS) involvement
• Bone marrow lymphoma cells involvement >20%, as assessed by bone marrow biopsy within 4 months before signing the ICF
• Has received radiation therapy to the pelvis
• Has a diagnosis of all leukemias including any type of CLL
• Active infection
• Pregnant or nursing
• Anticipated post-transplant chemotherapy and/or radiation therapy below the diaphragm
• Received any prior radio-immunotherapy
• Prior 1,3-bis(2-chloroethyl)-1-nitroso-urea (BCNU) within 6 weeks prior to first dose of G-CSF
• Prior cancer therapy, other investigational therapy within 4 weeks prior to first dose of G-CSF
• Prior granulocyte/macrophage-colony stimulating factor (GM-CSF) or pegfilgrastim within 3 weeks prior to the first dose of G-CSF
• Prior G-CSF within 2 weeks prior to the first dose of G-CSF
• Inadequate organ funtion evidenced by unacceptable laboratory result

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G-CSF + plerixafor; Patients will receive G-CSF for 4 mornings for mobilization, followed by another dose each morning before apheresis on days that the patient is to continue apheresis (up to 8 doses total). Patients will also receive plerixafor in the evening up to a maximum of 4 doses.	Drug: Granulocyte-colony stimulating factor (G-CSF); 10 µg/kg/day G-CSF, administered by subcutaneous (SC) injection; Other Names: GRAN®, Filgrastim; Drug: Plerixafor; 0.24 mg/kg/day subcutaneous injection; Other Names: Mozobil, AMD3100, GZ316455
Placebo Comparator: G-CSF + Placebo; Patients will receive G-CSF for 4 mornings for mobilization, followed by another dose each morning before apheresis on days that the patient is to continue apheresis (up to 8 doses total). Patients will also receive placebo in the evening up to a maximum of 4 doses.	Drug: Granulocyte-colony stimulating factor (G-CSF); 10 µg/kg/day G-CSF, administered by subcutaneous (SC) injection; Other Names: GRAN®, Filgrastim; Drug: Placebo; 0.24mg/kg/day placebo (0.9% Sodium Chloride) administered by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients who meet the target of ≥5 × 10^6 CD34+ cells/kg in 4 or fewer days of apheresis	Days 5- Day8

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients who achieve ≥2 × 10^6 CD34+ cells/kg within 4 or fewer days of apheresis	Day 5 - Day 8
Number of days of apheresis to collect ≥2 × 10^6 CD34+ cells/kg	Up to achieve the target of collecting ≥2 × 10^6 CD34+ cells/kg
Number of days of apheresis to collect ≥5 × 10^6 CD34+ cells/kg	Up to achieve the target of collecting ≥5 × 10^6 CD34+ cells/kg
Total number of CD34+ cells collected	Day 5 - Day 8
Time from transplantation to neutrophil and platelet (PLT) engraftment	up to 30 days post-transplantation
Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	from signed Informed Consent Form (ICF) to 30 days post-transplant and then ongoing as needed
Maximum plasma concentration (Cmax)	Day 4 - Day 5
Time to reach Cmax (Tmax)	Day 4 - Day 5
Area Under the Curve 0 to 10 hours post-dose (AUC0-10)	Day 4 - Day 5
Area Under the Curve 0 to last observed concentration (AUClast)	Day 4 - Day 5
Area Under the Curve (AUC)	Day 4 - Day 5
Percentage of extrapolation of AUC (AUCext)	Day 4 - Day 5
Half life (T1/2)	Day 4 - Day 5
Volume of distribution (Vz/F)	Day 4 - Day 5
Total body clearance (CL/F)	Day 4 - Day 5
Peripheral blood CD34+ cell counts (Pharmacodynamic analysis)	Day 4 - Day 5
The fold-increase in the number of circulating CD34+ following the first dose of plerixafor or placebo, with the first apheresis day (Day 5) value serving as the primary estimate	Day 5 - Day 8

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (Estimate): January 14, 2013

Study Record Updates

• Last Update Posted (Estimate): December 9, 2014
• Last Update Submitted That Met QC Criteria: December 8, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Immunologic Factors; Adjuvants, Immunologic; Lenograstim; Plerixafor
• Other Study ID Numbers: EFC12482; MOZ14409 (Other Identifier: Genzyme); U1111-1131-0145 (Other Identifier: UTN)