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

Neuroblastoma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01288573
• Other study ID #: DFI12860
• Secondary ID: 2010-019340-40MO
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 28, 2011
• Last updated: May 15, 2017
• Start date: March 3, 2014
• Est. completion date: May 9, 2017

Study information

• Verified date: May 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: May 9, 2017
• Est. primary completion date: May 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• plerixafor
160 µg/kg subcutaneous (SC) injection
• plerixafor
240 µg/kg subcutaneous (SC) injection
• plerixafor
320 µg/kg subcutaneous (SC) injection

Locations

Country	Name	City	State
Belgium	Investigational Site Number 51	Gent
Czechia	Investigational Site Number 81	Brno
Czechia	Investigational Site Number 82	Praha 5 - Motol
Denmark	Investigational Site Number 61	København Ø
France	Investigational Site Number 42	Lyon
France	Investigational Site Number 43	Paris Cedex 05
Germany	Investigational Site Number 33	Frankfurt Am Main
Germany	Investigational Site Number 34	Freiburg
Germany	Investigational Site Number 35	Hamburg
Germany	Investigational Site Number 31	Hannover
Germany	Investigational Site Number 36	München
Hungary	Investigational Site Number 83	Budapest
Israel	Investigational Site Number 92	Petach Tikva
Israel	Investigational Site Number 91	Tel-Aviv
Italy	Investigational Site Number 21	Genova
Italy	Investigational Site Number 24	Milano
Italy	Investigational Site Number 23	Padova
Italy	Investigational Site Number 22	Roma
Italy	Investigational Site Number 26	Torino
Netherlands	Investigational Site Number 72	Amsterdam
Netherlands	Investigational Site Number 71	Rotterdam
Poland	Investigational Site Number 85	Krakow
Poland	Investigational Site Number 84	Wroclaw
Spain	Investigational Site Number 94	Barcelona
Spain	Investigational Site Number 93	Madrid
United Kingdom	Investigational Site Number 11	Birmingham
United Kingdom	Investigational Site Number 13	Glasgow

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	Sanofi

Countries where clinical trial is conducted

Belgium,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2		Up to 5 days
Secondary	Number of days of apheresis required to reach =2 × 10^6 CD34+ cells/kg	During Stage 1 and Stage 2	Up to 5 days
Secondary	Yield of CD34+ cells for each apheresis	During Stage 1 and Stage 2	Up to 5 days
Secondary	Total CD34+ cell yield	During Stage 1 and Stage 2	Up to 5 days
Secondary	Percentage of patients proceeding to transplant	During Stage 1 and Stage 2	Within 6 months of last apheresis
Secondary	Percentage of patients successfully engrafting	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Secondary	Percentage of patients with durable engraftment	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Secondary	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)
Secondary	Duration of hospitalizations (planned or unplanned)	During Stage 1 and Stage 2	Throughout the duration of the study
Secondary	Mobilization of tumor cells into peripheral blood	During Stage 1 and Stage 2	Up to 5 days
Secondary	Relapse rates	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Secondary	Occurrence of secondary malignancies	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Secondary	Incidence of primary and secondary graft failure	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant
Secondary	Time to secondary graft failure	During Stage 1 and Stage 2	Up to 24 months post-transplant
Secondary	Survival rates	During Stage 1 and Stage 2	3, 6, 12 and 24 months post-transplant