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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Ewing's Sarcoma/Soft Tissue Sarcoma, Neuroblastoma, Brain Tumors

Intervention / Treatment
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* Drug: plerixafor
* Drug: plerixafor
* Drug: plerixafor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plerixafor 160 μg/kg<br>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). | Drug: plerixafor<br>* 160 μg/kg subcutaneous (SC) injection<br>|
| Experimental: Plerixafor 240 μg/kg<br>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). | Drug: plerixafor<br>* 240 μg/kg subcutaneous (SC) injection<br>|
| Experimental: Plerixafor 320 μg/kg<br>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). | Drug: plerixafor<br>* 320 μg/kg subcutaneous (SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2 |  | Up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg | During Stage 1 and Stage 2 | Up to 5 days | 
| Yield of CD34+ cells for each apheresis | During Stage 1 and Stage 2 | Up to 5 days | 
| Total CD34+ cell yield | During Stage 1 and Stage 2 | Up to 5 days | 
| Percentage of patients proceeding to transplant | During Stage 1 and Stage 2 | Within 6 months of last apheresis | 
| Percentage of patients successfully engrafting | During Stage 1 and Stage 2 | 3, 6, 12 and 24 months post-transplant | 
| Percentage of patients with durable engraftment | During Stage 1 and Stage 2 | 3, 6, 12 and 24 months post-transplant | 
| Summary of adverse events (AEs) | During Stage 1 and Stage 2 | 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) | 
| Duration of hospitalizations (planned or unplanned) | During Stage 1 and Stage 2 | Throughout the duration of the study | 
| Mobilization of tumor cells into peripheral blood | During Stage 1 and Stage 2 | Up to 5 days | 
| Relapse rates | During Stage 1 and Stage 2 | 3, 6, 12 and 24 months post-transplant | 
| Occurrence of secondary malignancies | During Stage 1 and Stage 2 | 3, 6, 12 and 24 months post-transplant | 
| Incidence of primary and secondary graft failure | During Stage 1 and Stage 2 | 3, 6, 12 and 24 months post-transplant | 
| Time to secondary graft failure | During Stage 1 and Stage 2 | Up to 24 months post-transplant | 
| Survival rates | During Stage 1 and Stage 2 | 3, 6, 12 and 24 months post-transplant |