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
- Brain TumorsNeuroblastomaEwing's Sarcoma/Soft Tissue Sarcoma
- Interventions
- Registration Number
- NCT01288573
- Lead Sponsor
- Genzyme, a Sanofi Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Plerixafor 240 μg/kg plerixafor 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). Plerixafor 160 μg/kg plerixafor 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). Plerixafor 320 μg/kg plerixafor 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).
- Primary Outcome Measures
Name Time Method Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2 Up to 5 days
- Secondary Outcome Measures
Name Time Method Summary of adverse events (AEs) 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) During Stage 1 and Stage 2
Duration of hospitalizations (planned or unplanned) Throughout the duration of the study During Stage 1 and Stage 2
Yield of CD34+ cells for each apheresis Up to 5 days During Stage 1 and Stage 2
Occurrence of secondary malignancies 3, 6, 12 and 24 months post-transplant During Stage 1 and Stage 2
Time to secondary graft failure Up to 24 months post-transplant During Stage 1 and Stage 2
Percentage of patients with durable engraftment 3, 6, 12 and 24 months post-transplant During Stage 1 and Stage 2
Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg Up to 5 days During Stage 1 and Stage 2
Percentage of patients proceeding to transplant Within 6 months of last apheresis During Stage 1 and Stage 2
Percentage of patients successfully engrafting 3, 6, 12 and 24 months post-transplant During Stage 1 and Stage 2
Survival rates 3, 6, 12 and 24 months post-transplant During Stage 1 and Stage 2
Total CD34+ cell yield Up to 5 days During Stage 1 and Stage 2
Mobilization of tumor cells into peripheral blood Up to 5 days During Stage 1 and Stage 2
Relapse rates 3, 6, 12 and 24 months post-transplant During Stage 1 and Stage 2
Incidence of primary and secondary graft failure 3, 6, 12 and 24 months post-transplant During Stage 1 and Stage 2
Trial Locations
- Locations (27)
Investigational Site Number 71
🇳🇱Rotterdam, Netherlands
Investigational Site Number 85
🇵🇱Krakow, Poland
Investigational Site Number 83
🇭🇺Budapest, Hungary
Investigational Site Number 43
🇫🇷Paris Cedex 05, France
Investigational Site Number 42
🇫🇷Lyon, France
Investigational Site Number 21
🇮🇹Genova, Italy
Investigational Site Number 31
🇩🇪Hannover, Germany
Investigational Site Number 13
🇬🇧Glasgow, United Kingdom
Investigational Site Number 94
🇪🇸Barcelona, Spain
Investigational Site Number 81
🇨🇿Brno, Czechia
Investigational Site Number 82
🇨🇿Praha 5 - Motol, Czechia
Investigational Site Number 91
🇮🇱Tel-Aviv, Israel
Investigational Site Number 93
🇪🇸Madrid, Spain
Investigational Site Number 35
🇩🇪Hamburg, Germany
Investigational Site Number 11
🇬🇧Birmingham, United Kingdom
Investigational Site Number 34
🇩🇪Freiburg, Germany
Investigational Site Number 61
🇩🇰København Ø, Denmark
Investigational Site Number 24
🇮🇹Milano, Italy
Investigational Site Number 23
🇮🇹Padova, Italy
Investigational Site Number 26
🇮🇹Torino, Italy
Investigational Site Number 22
🇮🇹Roma, Italy
Investigational Site Number 33
🇩🇪Frankfurt Am Main, Germany
Investigational Site Number 51
🇧🇪Gent, Belgium
Investigational Site Number 84
🇵🇱Wroclaw, Poland
Investigational Site Number 92
🇮🇱Petach Tikva, Israel
Investigational Site Number 72
🇳🇱Amsterdam, Netherlands
Investigational Site Number 36
🇩🇪München, Germany