Brain Tumors, Ewing's Sarcoma/Soft Tissue Sarcoma, Neuroblastoma
Conditions
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.
Interventions
DRUGplerixafor
160 μg/kg subcutaneous (SC) injection
Sponsors
Sanofi
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2 | Up to 5 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg | Up to 5 days | During Stage 1 and Stage 2 |
| Yield of CD34+ cells for each apheresis | Up to 5 days | During Stage 1 and Stage 2 |
| Total CD34+ cell yield | 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 |
| Percentage of patients with durable engraftment | 3, 6, 12 and 24 months post-transplant | During Stage 1 and Stage 2 |
| 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 |
| 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 |
| Occurrence of secondary malignancies | 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 |
| Time to secondary graft failure | Up to 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 |
Countries
Belgium, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, United Kingdom
Outcome results
None listed