A Multi-centre, Open Label, Single-arm Study Intended to Further Investigate the Safety and Efficacy of Plerixafor as a Front-line Mobilisation Agent in Combination With G-CSF in Patients With Lymphoma or MM (Multiple Myeloma).

NCT ID: NCT00838357

Last Updated: 2015-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2010-11-30

Brief Summary

This is a research study intended to further investigate the safety and efficacy of plerixafor in patients with NHL, HD, or MM. Patients who have previously failed stem cell mobilisation attempts or who have previously received more than one autologous or any allogeneic stem cell transplant are not eligible.

Detailed Description

Patients with advanced or treatment-refractory Multiple Myeloma (MM), Hodgkin's Disease (HD) and Non-Hodgkin's Lymphoma (NHL) may be successfully treated with high dose chemotherapy followed by autologous transplantation of peripheral blood stem cells (PBSCs). Successful engraftment of peripheral blood stem cells (PBSCs) is well correlated with the number of CD34+ cells infused.

Stem cell collection with plerixafor could have a major benefit by increasing the circulating number of PBSCs and decreasing the number of apheresis sessions required to collect a sufficient number of PBSCs for transplant.

This is a multi-centre, open label, single-arm study intended to further investigate the safety and efficacy of plerixafor in patients with NHL, HD, or MM. Patients who have previously failed stem cell mobilisation attempts or who have previously received more than one autologous or any allogeneic stem cell transplant are not eligible.

Screening for eligibility will take place up to 30 days before the first dose of G-CSF. Patients will receive a stem cell mobilisation regimen consisting of plerixafor and G-CSF. Patients will be given G-CSF for 4 consecutive days in the morning. Starting on the evening of Day 4, plerixafor will be administered subcutaneously (SC). The plerixafor dose will be timed to allow for a 10- to 11-hour interval between the plerixafor dosing and the initiation of apheresis. Patients may continue to receive the evening dose of plerixafor then G-CSF the next morning followed by apheresis for up to a total of 5 apheresis procedures until a minimum of at least 5 x 106 CD34+ cells/kg for NHL/HD or 6 x 106 CD34+ cells/kg for MM are collected. More cells may be collected if done within the 5 apheresis procedures. Stem cell collection will take place using standard procedures.

Following the last apheresis, patients will undergo pre-transplant myeloablative chemotherapy followed by transplantation of the collected autologous stem cells, using the established protocols and procedures at each site.

Peripheral blood samples will be collected for determining the number of CD34+ cells in the peripheral blood. In addition, a sample will be obtained from each apheresis product to determine the quantity of CD34+ cells collected after each procedure.

Safety data will be reported according to guidelines provided in the protocol. Adverse event (AE) guidance is summarised in the protocol. Investigators will grade AEs using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.

Efficacy will be based on the quantity of CD34+ cells harvested and the subsequent engraftment and graft status. Patients who undergo haematopoietic stem cell transplantation will be monitored for graft status at 100 days, 6 months, and 12 months.

Conditions

Lymphoma (Non-Hodgkin's Lymphoma); Hodgkin's Disease or Multiple Myeloma; Front Line Mobilization; Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Plerixafor

Plerixafor added to a G-CSF Mobilisation regimen

Group Type: EXPERIMENTAL

Generic = Plerixafor

Intervention Type: DRUG

240µg/kg administered as an SC injection 10 to 11 hours prior to initiation of apheresis. Daily administration for 1 up to 5 consecutive days

Interventions

Generic = Plerixafor

240µg/kg administered as an SC injection 10 to 11 hours prior to initiation of apheresis. Daily administration for 1 up to 5 consecutive days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of MM, NHL, or HD in partial response (PR) or complete response (CR)
• Eligible and planned for an autologous haematopoietic stem cell transplantation
• Written informed consent
• At least 18 years of age (inclusive)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• White blood cell (WBC) count ≥2.5 x 10^9/L
• Absolute neutrophil count (ANC) ≥1.5 x 10^9 /L
• Platelet count ≥100 x 10^9/L
• Serum creatinine ≤2.2 mg/dL
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT), and total bilirubin <2.5 x upper limit of normal (ULN)
• Adequate cardiac, renal, and pulmonary function sufficient to undergo apheresis and transplantation, i.e., eligible by institutional standards for autologous stem cell transplant
• All patients must agree to use a highly effective method of contraception whilst 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). Effective birth control includes: a) birth control pills, depot progesterone, or an intrauterine device plus one barrier method, or b) two barrier methods. Effective barrier methods are: male and female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). For patients using a hormonal contraceptive method, information about any interaction of plerixafor with hormonal contraceptives is not known.

Exclusion Criteria

• History of any acute or chronic leukaemia (including myelodysplastic syndrome)
• Prior allogeneic transplantation or more than one prior autologous transplantation
• Failed previous CD34+ cell collection attempts (either due to insufficient yield in apheresis product, or ineligible for apheresis because of inadequate mobilisation of CD34+ cells into peripheral blood)
• Less than 4 weeks since last anti-cancer therapy (including chemotherapy, biologic/immunologic, radiation) or less than 6 weeks if prior therapy with nitrosourea or mitomycin (for therapies with long-acting agents, a treatment-free interval of at least 2 half-lives should be considered) with the exception of ; Treatment with thalidomide, dexamethasone, lenalidomide (Revlimid®), and/or bortezomib (Velcade®) which is allowed up to 7 days prior to the first dose of G-CSF.
• Bone marrow involvement >20% assessed based on the most recent bone marrow aspirate or biopsy
• Treated with G-CSF or other cytokine within 14 days prior to the first dose of G-CSF for mobilisation
• Known to be human immunodeficiency virus (HIV) positive
• Active hepatitis B or hepatitis C
• Acute infection (febrile, i.e., temperature >38°C) within 24 hours prior to dosing or antibiotic therapy within 7 days prior to the first dose of G-CSF
• Hypercalcaemia as evidenced by >1 mg/dL above ULN
• Previously received investigational therapy within 4 weeks of enrolling in this protocol or currently enrolled in another investigational protocol during the mobilisation phase
• Central nervous system involvement including brain metastases or leptomeningeal disease
• Pregnant or nursing women
• Electrocardiogram (ECG) or study result (exercise study, scan) indicative of cardiac ischaemia or a history of clinically significant rhythm disturbance (arrhythmias), or other conduction abnormality in the last year that in the opinion of the Investigator warrants exclusion of the subject from the trial.
• Co-morbid condition(s), which in the opinion of the Investigator, renders the patient at high risk from treatment complications or impairs their ability to comply with the study treatment and protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme Europe B.V.

Locations

Hôpital du Haut Lévêque

Bordeaux, , France

Hôpital Lyon Sud

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

CHU Hotel-Dieu Université de Nantes

Nantes, , France

Hôpital Saint-Louis

Paris, , France

Institut Gustave Roussy

Villejuif, , France

Charité - Campus Benjamin Franklin

Berlin, , Germany

Klinikum der Universität zu Köln

Cologne, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Klinikum Nürnberg Nord

Nuremberg, , Germany

Universitätsklinik Würzburg

Würzburg, , Germany

L. & A. Seragnoli, University of Bologna

Bologna, , Italy

Ospedale Ferrarotto

Catania, , Italy

Azienda Ospedaliera S. Martino

Genova, , Italy

VU Medisch Centrum

Amsterdam, , Netherlands

Hospital Santa Creu y Sant Pau

Barcelona, , Spain

Hospital Carlos-Haya

Málaga, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital la Fe

Valencia, , Spain

Karolinska Universitetssjukhuset Huddinge

Stockholm, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Gartnavel Hospital

Glasgow, , United Kingdom

St James's University Hospital

Leeds, , United Kingdom

King's college Hospital

London, , United Kingdom

Nottingham University NHS Trust

Nottingham, , United Kingdom

Countries

France; Germany; Italy; Netherlands; Spain; Sweden; United Kingdom

Other Identifiers

2008-000689-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOZ00808

Identifier Type: -

Identifier Source: org_study_id