a combined study in pediatric cancer patients for dose ranging and efficacy/safety of plerixafor plus standard regimens for mobilization versus standard regimens alone

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

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 \ 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