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

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01288573
• Collaborator: Sanofi (Industry)
• Enrollment: 46
• Locations: 27
• Arms: 3
• Duration (Months): 38.2
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ewing's Sarcoma/Soft Tissue Sarcoma; Neuroblastoma; Brain Tumors	Drug: plerixafor; Drug: plerixafor; Drug: plerixafor	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Study Start Date: Mar 3, 2014
• Actual Primary Completion Date: May 9, 2017
• Actual Study Completion Date: May 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Plerixafor 160 μg/kg 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; 160 μg/kg subcutaneous (SC) injection
Experimental: Plerixafor 240 μg/kg 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; 240 μg/kg subcutaneous (SC) injection
Experimental: Plerixafor 320 μg/kg 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; 320 μg/kg subcutaneous (SC) injection

Outcome Measures

Primary Outcome Measures

1. Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2 [Up to 5 days]

Secondary Outcome Measures

1. Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg [Up to 5 days]

   During Stage 1 and Stage 2

2. Yield of CD34+ cells for each apheresis [Up to 5 days]

   During Stage 1 and Stage 2

3. Total CD34+ cell yield [Up to 5 days]

   During Stage 1 and Stage 2

4. Percentage of patients proceeding to transplant [Within 6 months of last apheresis]

   During Stage 1 and Stage 2

5. Percentage of patients successfully engrafting [3, 6, 12 and 24 months post-transplant]

   During Stage 1 and Stage 2

6. Percentage of patients with durable engraftment [3, 6, 12 and 24 months post-transplant]

   During Stage 1 and Stage 2

7. 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

8. Duration of hospitalizations (planned or unplanned) [Throughout the duration of the study]

   During Stage 1 and Stage 2

9. Mobilization of tumor cells into peripheral blood [Up to 5 days]

   During Stage 1 and Stage 2

10. Relapse rates [3, 6, 12 and 24 months post-transplant]

    During Stage 1 and Stage 2

11. Occurrence of secondary malignancies [3, 6, 12 and 24 months post-transplant]

    During Stage 1 and Stage 2

12. Incidence of primary and secondary graft failure [3, 6, 12 and 24 months post-transplant]

    During Stage 1 and Stage 2

13. Time to secondary graft failure [Up to 24 months post-transplant]

    During Stage 1 and Stage 2

14. Survival rates [3, 6, 12 and 24 months post-transplant]

    During Stage 1 and Stage 2

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 18 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 51	Gent		Belgium	9000
2	Investigational Site Number 81	Brno		Czechia	62500
3	Investigational Site Number 82	Praha 5 - Motol		Czechia	15006
4	Investigational Site Number 61	København Ø		Denmark	2100
5	Investigational Site Number 42	Lyon		France	69373
6	Investigational Site Number 43	Paris Cedex 05		France	75248
7	Investigational Site Number 33	Frankfurt Am Main		Germany	60590
8	Investigational Site Number 34	Freiburg		Germany	79106
9	Investigational Site Number 35	Hamburg		Germany	20246
10	Investigational Site Number 31	Hannover		Germany	30625
11	Investigational Site Number 36	München		Germany	80337
12	Investigational Site Number 83	Budapest		Hungary	1097
13	Investigational Site Number 92	Petach Tikva		Israel	4920235
14	Investigational Site Number 91	Tel-Aviv		Israel	64239
15	Investigational Site Number 21	Genova		Italy	16100
16	Investigational Site Number 24	Milano		Italy	20133
17	Investigational Site Number 23	Padova		Italy	35128
18	Investigational Site Number 22	Roma		Italy	00165
19	Investigational Site Number 26	Torino		Italy	10126
20	Investigational Site Number 72	Amsterdam		Netherlands	1105 AZ
21	Investigational Site Number 71	Rotterdam		Netherlands	3015 GJ
22	Investigational Site Number 85	Krakow		Poland	30-663
23	Investigational Site Number 84	Wroclaw		Poland	50-368
24	Investigational Site Number 94	Barcelona		Spain	08035
25	Investigational Site Number 93	Madrid		Spain	28009
26	Investigational Site Number 11	Birmingham		United Kingdom	B4 6NH
27	Investigational Site Number 13	Glasgow		United Kingdom	G51 4TF

Sponsors and Collaborators

• Genzyme, a Sanofi Company
• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01288573
• Other Study ID Numbers: DFI12860; 2010-019340-40; MOZ15609
• First Posted: Feb 2, 2011
• Last Update Posted: May 16, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Sarcoma; Neuroblastoma; Sarcoma, Ewing; Plerixafor

Study Results

No Results Posted as of May 16, 2017