An Exploratory Safety Study to Investigate the Extent of Tumor Cell Mobilization (TCM) After Use of G-CSF Alone or G-CSF Plus Plerixafor in Multiple Myeloma (MM) Patients Who May be Poor Mobilizers of Stem Cells

A Pilot, Exploratory, Randomized, Phase 2 Safety Study Evaluating Tumor Cell (Plasma Cell) Mobilization and Apheresis Product Contamination in Plerixafor Plus Non-pegylated G-CSF Mobilized Patients and in Non-pegylated G-CSF Alone Mobilized Patients

The primary objective of this study is to evaluate tumor cell mobilization (TCM) with non-pegylated G-CSF alone compared with non-pegylated G-CSF plus plerixafor in patients with multiple myeloma (MM) who are potentially poor mobilizers of hematopoietic stem cells (HSC).

Second objectives are to evaluate survival and disease status of G-CSF alone compared with GCSF plus plerixafor, and the efficacy and safety of G-CSF plus plerixafor when used to mobilize stem cells for autologous transplantation.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Granulocyte-colony stimulating factor (G-CSF); Drug: Plerixafor

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, B-8000
    • Investigational Site Number 056002
• Estonia
  • Tallinn, Estonia, 13419
    • Investigational Site Number 233001
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Investigational Site Number 440001
• Sweden
  • Stockholm, Sweden, 14186
    • Investigational Site Number 752001
  • Umeå, Sweden, 901 85
    • Investigational Site Number 752002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of MM in partial response or complete response, who are undergo an autologous hematopoietic stem cell transplantation and could be considered potentially poor mobilizers.

Exclusion Criteria:

• Does not have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has a history of any acute or chronic leukemia (including myelodysplastic syndrome).
• Had prior allogeneic or autologous transplantation.
• Less than 3 to 6 weeks since last anti-cancer therapy.
• Chemotherapy for mobilization is not allowed.
• Has bone marrow involvement >10% assessed based on the most recent bone marrow aspirate or biopsy performed prior to first dose of G-CSF.
• Was treated with G-CSF or other cytokine within 14 days prior to the first dose of G-CSF for mobilization.
• Has previously received plerixafor.
• Is known to be HIV positive.
• Has active hepatitis B or hepatitis C.
• Has an acute infection within 24 hours prior to dosing or antibiotic therapy within 7 days prior to the first dose of G-CSF.
• Has hypercalcaemia as evidenced by >1 mg/dL above upper limit of normal (ULN).
• Previously received investigational therapy within 4 weeks of screening in this protocol or currently enrolled in another investigational protocol during the mobilization phase.
• Has central nervous system involvement including brain metastases or leptomeningeal disease.
• Has an electrocardiogram (ECG) or study result indicative of cardiac ischemia or a history of clinically significant rhythm disturbance(arrhythmias), or other conduction abnormality.
• Has co-morbid condition(s), which may render the patient at high risk from treatment complications or impairs his/her ability to comply with the study treatment and protocol.
• Has a white blood cell (WBC) count <2.5 x 10^9/L.
• Has an absolute neutrophil count (ANC) <1.5 x 10^9/L.
• Has a platelet count <100 x 10^9/L.
• Has an estimated creatine clearance ≤50 mL/min.
• Has aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT), and total bilirubin ≥2.5 x ULN.
• Does not have adequate cardiac, and pulmonary function sufficient to undergo apheresis and transplantation.
• Pregnant or breastfeeding women.
• Does not agree to use a highly effective method of contraception while on study treatment and for at least 3 months following study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: G-CSF alone; Patients will receive G-CSF for 5 consecutive days	Drug: Granulocyte-colony stimulating factor (G-CSF); 10 mcg/kg, solution, subcutaneous injection
Experimental: G-CSF plus plerixafor; Patients will receive G-CSF for 4 consecutive days, then receive plerixafor before the 5th dose of G-CSF	Drug: Granulocyte-colony stimulating factor (G-CSF); 10 mcg/kg, solution, subcutaneous injection; Drug: Plerixafor; 240mcg/kg, solution, subcutaneous injection; Other Names: Mozobil,AMD3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The presence of myeloma tumor cells as measured by the percentage of myeloma tumor cells/CD34+ cells	Peripheral blood parameters	Day 1 to Day 8 of the apheresis/treatment period
The presence of myeloma tumor cells as measured by the percentage of myeloma tumor cells/plerixafor cumulative dose/kg body weights	Peripheral blood parameters	Day 5 to Day 8 of the apheresis/treatment period
The presence of myeloma tumor cells as measured by the percentage of myeloma tumor cells/G-CSF cumulative dose/kg body weight	Peripheral blood parameters	Day 5 to Day 8 of the apheresis/treatment period
The change in tumor cell mobilization(TCM) in the peripheral blood	Peripheral blood parameters	Day 4 pre-G-CSF to Day 5 pre-G-CSF
The number of myeloma tumor cells per patient at each apheresis	Apheresis product parameters	Day 1 to Day 8 of the apheresis/treatment period
The number of patients who mobilize at least 4.5x10^5 myeloma tumor cells/kg body weight as measured in each apheresis product	Apheresis product parameters	Day 5 to Day 8 of the apheresis/treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
CD34+ stem cell yield in the apheresis product	Day 1 to Day 8 of the apheresis/treatment period
The number of patients that proceed to transplantation	Up to 2 months after final apheresis
Overall survival	Day 100 post transplant and up to 2 years post first-G-CSF dose

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 17, 2012
• First Posted (Estimate): December 20, 2012

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Hematopoietic stem cell transplantation; Tumour cell mobilization
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; 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: ARD12858; MOZ23510 (Other Identifier: Genzyme); 2011-004783-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No