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

NCT ID: NCT01288573

Last Updated: 2017-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-03
• Study Completion Date: 2017-05-09

Brief Summary

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.

Conditions

Ewing's Sarcoma/Soft Tissue Sarcoma; Neuroblastoma; Brain Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

plerixafor

Intervention Type: DRUG

160 μg/kg subcutaneous (SC) injection

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).

Group Type: EXPERIMENTAL

plerixafor

Intervention Type: DRUG

240 μg/kg subcutaneous (SC) injection

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).

Group Type: EXPERIMENTAL

plerixafor

Intervention Type: DRUG

320 μg/kg subcutaneous (SC) injection

Interventions

plerixafor

160 μg/kg subcutaneous (SC) injection

Intervention Type: DRUG

plerixafor

240 μg/kg subcutaneous (SC) injection

Intervention Type: DRUG

plerixafor

320 μg/kg subcutaneous (SC) injection

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 51

Ghent, , Belgium

Investigational Site Number 81

Brno, , Czechia

Investigational Site Number 82

Praha 5 - Motol, , Czechia

Investigational Site Number 61

København Ø, , Denmark

Investigational Site Number 42

Lyon, , France

Investigational Site Number 43

Paris, , France

Investigational Site Number 33

Frankfurt am Main, , Germany

Investigational Site Number 34

Freiburg im Breisgau, , Germany

Investigational Site Number 35

Hamburg, , Germany

Investigational Site Number 31

Hanover, , Germany

Investigational Site Number 36

München, , Germany

Investigational Site Number 83

Budapest, , Hungary

Investigational Site Number 92

Petah Tikva, , Israel

Investigational Site Number 91

Tel Aviv, , Israel

Investigational Site Number 21

Genova, , Italy

Investigational Site Number 24

Milan, , Italy

Investigational Site Number 23

Padua, , Italy

Investigational Site Number 22

Roma, , Italy

Investigational Site Number 26

Torino, , Italy

Investigational Site Number 72

Amsterdam, , Netherlands

Investigational Site Number 71

Rotterdam, , Netherlands

Investigational Site Number 85

Krakow, , Poland

Investigational Site Number 84

Wroclaw, , Poland

Investigational Site Number 94

Barcelona, , Spain

Investigational Site Number 93

Madrid, , Spain

Investigational Site Number 11

Birmingham, , United Kingdom

Investigational Site Number 13

Glasgow, , United Kingdom

Countries

Belgium; Czechia; Denmark; France; Germany; Hungary; Israel; Italy; Netherlands; Poland; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36163427 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32127657 (View on PubMed)

Other Identifiers

2010-019340-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOZ15609

Identifier Type: OTHER

Identifier Source: secondary_id

DFI12860

Identifier Type: -

Identifier Source: org_study_id