Clinical trial NCT01288573: A Combined Study in Pediatric Cancer Patients for Dose Ranging and Efficacy/Safety of Plerixafor Plus Standard Regimens for Mobilization Versus Standard Regimens Alone
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ewing's Sarcoma/Soft Tissue Sarcoma
Neuroblastoma
Brain Tumors
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2011-02-02
Enrollment: 46
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2
timeFrame: Up to 5 days
Secondary outcomes:
measure: Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg
timeFrame: Up to 5 days
measure: Yield of CD34+ cells for each apheresis
timeFrame: Up to 5 days
measure: Total CD34+ cell yield
timeFrame: Up to 5 days
measure: Percentage of patients proceeding to transplant
timeFrame: Within 6 months of last apheresis
measure: Percentage of patients successfully engrafting
timeFrame: 3, 6, 12 and 24 months post-transplant
measure: Percentage of patients with durable engraftment
timeFrame: 3, 6, 12 and 24 months post-transplant
measure: Summary of adverse events (AEs)
timeFrame: 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)
measure: Duration of hospitalizations (planned or unplanned)
timeFrame: Throughout the duration of the study
measure: Mobilization of tumor cells into peripheral blood
timeFrame: Up to 5 days
measure: Relapse rates
timeFrame: 3, 6, 12 and 24 months post-transplant
measure: Occurrence of secondary malignancies
timeFrame: 3, 6, 12 and 24 months post-transplant
measure: Incidence of primary and secondary graft failure
timeFrame: 3, 6, 12 and 24 months post-transplant
measure: Time to secondary graft failure
timeFrame: Up to 24 months post-transplant
measure: Survival rates
timeFrame: 3, 6, 12 and 24 months post-transplant
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Investigational Site Number 51
city: Brno
country: Czechia
facility: Investigational Site Number 81
city: Praha 5 - Motol
country: Czechia
facility: Investigational Site Number 82
city: København Ø
country: Denmark
facility: Investigational Site Number 61
city: Lyon
country: France
facility: Investigational Site Number 42
city: Paris Cedex 05
country: France
facility: Investigational Site Number 43
city: Frankfurt Am Main
country: Germany
facility: Investigational Site Number 33
city: Freiburg
country: Germany
facility: Investigational Site Number 34
city: Hamburg
country: Germany
facility: Investigational Site Number 35
city: Hannover
country: Germany
facility: Investigational Site Number 31
city: München
country: Germany
facility: Investigational Site Number 36
city: Budapest
country: Hungary
facility: Investigational Site Number 83
city: Petach Tikva
country: Israel
facility: Investigational Site Number 92
city: Tel-Aviv
country: Israel
facility: Investigational Site Number 91
city: Genova
country: Italy
facility: Investigational Site Number 21
city: Milano
country: Italy
facility: Investigational Site Number 24
city: Padova
country: Italy
facility: Investigational Site Number 23
city: Roma
country: Italy
facility: Investigational Site Number 22
city: Torino
country: Italy
facility: Investigational Site Number 26
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 72
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 71
city: Krakow
country: Poland
facility: Investigational Site Number 85
city: Wroclaw
country: Poland
facility: Investigational Site Number 84
city: Barcelona
country: Spain
facility: Investigational Site Number 94
city: Madrid
country: Spain
facility: Investigational Site Number 93
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 11
city: Glasgow
country: United Kingdom
facility: Investigational Site Number 13
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.