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

Genzyme

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: plerixafor

Study type: Interventional

Funder types: Industry

Identifiers

NCT01288573

DFI12860

2010-019340-40 (EudraCT Number)

MOZ15609 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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46 participants in 3 patient groups

Plerixafor 160 μg/kg

Experimental group

Description:

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).

Treatment:

Drug: plerixafor

Drug: plerixafor

Drug: plerixafor

Plerixafor 240 μg/kg

Experimental group

Description:

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).

Treatment:

Drug: plerixafor

Drug: plerixafor

Drug: plerixafor

Plerixafor 320 μg/kg

Experimental group

Description:

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).

Treatment:

Drug: plerixafor

Drug: plerixafor

Drug: plerixafor