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.

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