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

NCT01288573 | Completed Phase 1 DMC

• 3 other identifiers: DFI128602010-019340-40MOZ15609
• Study Type: interventional
• Target: 46
• Locations: 12 countries
• Sites: 27

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

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2

  Up to 5 days

Secondary Outcomes (14)

• Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg

  Up to 5 days

• Yield of CD34+ cells for each apheresis

  Up to 5 days

• Total CD34+ cell yield

  Up to 5 days

• Percentage of patients proceeding to transplant

  Within 6 months of last apheresis

• Percentage of patients successfully engrafting

  3, 6, 12 and 24 months post-transplant

Study Arms (3)

Plerixafor 160 μg/kg

EXPERIMENTAL

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

Plerixafor 240 μg/kg

EXPERIMENTAL

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

Plerixafor 320 μg/kg

EXPERIMENTAL

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

Interventions

plerixafor DRUG

160 μg/kg subcutaneous (SC) injection

Plerixafor 160 μg/kg

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• Sanofi: collaborator

Study Sites (27)

Investigational Site Number 51

Ghent, 9000, Belgium

Location

Investigational Site Number 81

Brno, 62500, Czechia

Location

Investigational Site Number 82

Praha 5 - Motol, 15006, Czechia

Location

Investigational Site Number 61

København Ø, 2100, Denmark

Location

Investigational Site Number 42

Lyon, 69373, France

Location

Investigational Site Number 43

Paris, 75248, France

Location

Investigational Site Number 33

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number 34

Freiburg im Breisgau, 79106, Germany

Location

Investigational Site Number 35

Hamburg, 20246, Germany

Location

Investigational Site Number 31

Hanover, 30625, Germany

Location

Investigational Site Number 36

München, 80337, Germany

Location

Investigational Site Number 83

Budapest, 1097, Hungary

Location

Investigational Site Number 92

Petah Tikva, 4920235, Israel

Location

Investigational Site Number 91

Tel Aviv, 64239, Israel

Location

Investigational Site Number 21

Genova, 16100, Italy

Location

Investigational Site Number 24

Milan, 20133, Italy

Location

Investigational Site Number 23

Padua, 35128, Italy

Location

Investigational Site Number 22

Roma, 00165, Italy

Location

Investigational Site Number 26

Torino, 10126, Italy

Location

Investigational Site Number 72

Amsterdam, 1105 AZ, Netherlands

Location

Investigational Site Number 71

Rotterdam, 3015 GJ, Netherlands

Location

Investigational Site Number 85

Krakow, 30-663, Poland

Location

Investigational Site Number 84

Wroclaw, 50-368, Poland

Location

Investigational Site Number 94

Barcelona, 08035, Spain

Location

Investigational Site Number 93

Madrid, 28009, Spain

Location

Investigational Site Number 11

Birmingham, B4 6NH, United Kingdom

Location

Investigational Site Number 13

Glasgow, G51 4TF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36163427 DERIVED

• 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.

  PMID: 32127657 DERIVED

MeSH Terms

Conditions

Neuroblastoma; Brain Neoplasms

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2011
• First Posted: February 2, 2011
• Study Start: March 3, 2014
• Primary Completion: May 9, 2017
• Study Completion: May 9, 2017
• Last Updated: May 16, 2017

Record last verified: 2017-05

Locations

ES (2); GB (2); DK (1); CZ (2); BE (1); IT (5); HU (1); IL (2); NL (2); FR (2); DE (5); PL (2)