A Combined Study in Pediatric Cancer Patients for Dose Ranging and Efficacy/Safety of Plerixafor Plus Standard Regimens for Mobilization Versus Standard Regimens Alone

A Phase 1/2 Combined Dose Ranging and Randomized, Open-label, Comparative Study of the Efficacy and Safety of Plerixafor in Addition to Standard Regimens for Mobilization of Haematopoietic Stem Cells Into Peripheral Blood, and Subsequent Collection by Apheresis, Versus Standard Mobilization Regimens Alone in Pediatric Patients, Aged 1 to <18 Years, With Solid Tumours Eligible for Autologous Transplants.

This is a multi-site study with plerixafor in pediatric cancer patients. The study will be conducted in 2 stages:

• Stage 1 is a dose-escalation study.
• Stage 2 is an open-label, randomized, comparative study using the appropriate dosing regimen identified in the Stage 1 dose-escalation study.

All participating patients will receive a standard mobilization regimen as per study site practice guidelines (either chemotherapy plus once daily granulocyte-colony stimulating factor (G-CSF) or once daily G-CSF alone). The only change to the standard mobilization regimen is the addition of plerixafor treatment prior to apheresis for all patients in Stage 1 (dose escalation), and for those patients randomized to the plerixafor plus standard mobilization treatment arm in Stage 2 (randomized, comparative).

Stage 1 will enroll at least 27 patients. Stage 2 will enroll at least 40 patients.

Study Overview

• Status: Completed
• Conditions: Neuroblastoma; Brain Tumors; Ewing's Sarcoma/Soft Tissue Sarcoma
• Intervention / Treatment: Drug: plerixafor; Drug: plerixafor; Drug: plerixafor

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Investigational Site Number 51
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number 81
  • Praha 5 - Motol, Czechia, 15006
    • Investigational Site Number 82
• Denmark
  • København Ø, Denmark, 2100
    • Investigational Site Number 61
• France
  • Lyon, France, 69373
    • Investigational Site Number 42
  • Paris Cedex 05, France, 75248
    • Investigational Site Number 43
• Germany
  • Frankfurt Am Main, Germany, 60590
    • Investigational Site Number 33
  • Freiburg, Germany, 79106
    • Investigational Site Number 34
  • Hamburg, Germany, 20246
    • Investigational Site Number 35
  • Hannover, Germany, 30625
    • Investigational Site Number 31
  • München, Germany, 80337
    • Investigational Site Number 36
• Hungary
  • Budapest, Hungary, 1097
    • Investigational Site Number 83
• Israel
  • Petach Tikva, Israel, 4920235
    • Investigational Site Number 92
  • Tel-Aviv, Israel, 64239
    • Investigational Site Number 91
• Italy
  • Genova, Italy, 16100
    • Investigational Site Number 21
  • Milano, Italy, 20133
    • Investigational Site Number 24
  • Padova, Italy, 35128
    • Investigational Site Number 23
  • Roma, Italy, 00165
    • Investigational Site Number 22
  • Torino, Italy, 10126
    • Investigational Site Number 26
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Investigational Site Number 72
  • Rotterdam, Netherlands, 3015 GJ
    • Investigational Site Number 71
• Poland
  • Krakow, Poland, 30-663
    • Investigational Site Number 85
  • Wroclaw, Poland, 50-368
    • Investigational Site Number 84
• Spain
  • Barcelona, Spain, 08035
    • Investigational Site Number 94
  • Madrid, Spain, 28009
    • Investigational Site Number 93
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Investigational Site Number 11
  • Glasgow, United Kingdom, G51 4TF
    • Investigational Site Number 13

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 2 to < 18 years during stage 1 and 1 to < 18 years during stage 2
• Ewing's sarcoma, soft tissue sarcoma, lymphoma, neuroblastoma, brain tumors or other malignancy (excluding any form of leukemia) requiring treatment with high dose chemotherapy and autologous transplant as rescue therapy
• Eligible for autologous transplantation
• Recovered from all acute significant toxic effects of prior chemotherapy
• Adequate performance status (for patients ≥16 years of age, defined as Karnofsky score >60 and for patients <16 years of age, defined as Lansky score >60)
• Absolute neutrophil count >0.75 × 10^9/L
• Platelet count >50 × 10^9/L
• Calculated creatinine clearance (using the Schwartz method): during study Stage 1, >80 mL/min/1.73m^2 and during study Stage 2, >60 mL/min/1.73m^2
• Aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase(SGOT), alanine aminotransferase(ALT)/serum glutamic pyruvic transaminase (SGPT) and total bilirubin <3 × upper limit of normal
• The patient and/or their parent/legal guardian is willing and able to provide signed informed consent
• Patients who are sexually active must be willing to abstain from sexual intercourse or agree to use an approved form of contraception while receiving plerixafor and/or standard mobilization treatment and for at least 3 months following any plerixafor treatment

Exclusion Criteria:

• Any form of leukemia
• A co-morbid condition which, in the view of the Investigator, renders the patient at high-risk from treatment complications
• Previous stem cell transplantation
• Persistent high percentage marrow involvement prior to mobilization will be prohibited.
• On-going toxicities (excluding alopecia) Grade ≥2 resulting from prior chemotherapy
• Acute infection
• Fever (temperature >38.5°C) - if fever is between 37°C and 38.5°C, infection must be excluded as a cause
• Known HIV seropositivity, AIDS, hepatitis C or active hepatitis B infections
• Positive pregnancy test in post pubertal girls
• History of clinically significant cardiac abnormality or arrhythmia
• Use of an investigational drug which is not approved in any indication either in adults or pediatrics within 2 weeks prior to the first dose of G-CSF to be administered as part of the patient's planned standard mobilization regimen, and/or during the study up until engraftment of the transplant. If patients are on investigational drugs as part of their anti-cancer regimen, this should be discussed with the Sponsor before screening. Drugs approved for other indications that are being used in a manner considered standard of care for this transplant procedure are allowed
• The patient (and/or their parent/legal guardian), in the opinion of the Investigator, is unable to adhere to the requirements of the study

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plerixafor 160 μg/kg; Patients will receive subcutaneous (SC) injection of 160 μg/kg plerixafor in addition to their standard mobilization regimen. Each dose of plerixafor will be administered in the evening 9 to 11 hours prior to apheresis (up to a maximum of 5 apheresis sessions).	Drug: plerixafor; 160 μg/kg subcutaneous (SC) injection; Drug: plerixafor; 240 μg/kg subcutaneous (SC) injection; Drug: plerixafor; 320 μg/kg subcutaneous (SC) injection
Experimental: Plerixafor 240 μg/kg; Patients will receive subcutaneous (SC) injection of 240 μg/kg plerixafor in addition to their standard mobilization regimen. Each dose of plerixafor will be administered in the evening 9 to 11 hours prior to apheresis (up to a maximum of 5 apheresis sessions).	Drug: plerixafor; 160 μg/kg subcutaneous (SC) injection; Drug: plerixafor; 240 μg/kg subcutaneous (SC) injection; Drug: plerixafor; 320 μg/kg subcutaneous (SC) injection
Experimental: Plerixafor 320 μg/kg; Patients will receive subcutaneous (SC) injection of 320 μg/kg plerixafor in addition to their standard mobilization regimen. Each dose of plerixafor will be administered in the evening 9 to 11 hours prior to apheresis (up to a maximum of 5 apheresis sessions).	Drug: plerixafor; 160 μg/kg subcutaneous (SC) injection; Drug: plerixafor; 240 μg/kg subcutaneous (SC) injection; Drug: plerixafor; 320 μg/kg subcutaneous (SC) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2	Up to 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg	During Stage 1 and Stage 2	Up to 5 days
Yield of CD34+ cells for each apheresis	During Stage 1 and Stage 2	Up to 5 days
Total CD34+ cell yield	During Stage 1 and Stage 2	Up to 5 days
Percentage of patients proceeding to transplant	During Stage 1 and Stage 2	Within 6 months of last apheresis
Percentage of patients successfully engrafting	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Percentage of patients with durable engraftment	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Summary of adverse events (AEs)	During Stage 1 and Stage 2	Up to 24 months after last transplant or 24 months after last dose (for patients that do not transplant within 6 months of last apheresis)
Duration of hospitalizations (planned or unplanned)	During Stage 1 and Stage 2	Throughout the duration of the study
Mobilization of tumor cells into peripheral blood	During Stage 1 and Stage 2	Up to 5 days
Relapse rates	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Occurrence of secondary malignancies	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Incidence of primary and secondary graft failure	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Time to secondary graft failure	During Stage 1 and Stage 2	Up to 24 months post-transplant
Survival rates	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Sebastien B, Cheverton P, Magnin C, Aouni J, Castan R. Development and validation of a predictive model to guide the use of plerixafor in pediatric population. Bone Marrow Transplant. 2022 Dec;57(12):1827-1832. doi: 10.1038/s41409-022-01831-2. Epub 2022 Sep 26.
• Morland B, Kepak T, Dallorso S, Sevilla J, Murphy D, Luksch R, Yaniv I, Bader P, Rossler J, Bisogno G, Maecker-Kolhoff B, Lang P, Zwaan CM, Sumerauer D, Krivan G, Bernard J, Liu Q, Doyle E, Locatelli F. Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC). Bone Marrow Transplant. 2020 Sep;55(9):1744-1753. doi: 10.1038/s41409-020-0836-2. Epub 2020 Mar 3.

Study record dates

Study Major Dates

• Study Start: March 3, 2014
• Primary Completion (Actual): May 9, 2017
• Study Completion (Actual): May 9, 2017

Study Registration Dates

• First Submitted: January 28, 2011
• First Submitted That Met QC Criteria: February 1, 2011
• First Posted (Estimate): February 2, 2011

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma; Sarcoma, Ewing; Neuroblastoma; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: DFI12860; 2010-019340-40 (EudraCT Number); MOZ15609 (Other Identifier: Genzyme other study code)