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 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:
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Stage 1 is a dose-escalation study.
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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 |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
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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
- Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2 [Up to 5 days]
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 2 to < 18 years during stage 1 and 1 to < 18 years during stage 2
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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
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Eligible for autologous transplantation
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Recovered from all acute significant toxic effects of prior chemotherapy
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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)
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Absolute neutrophil count >0.75 × 10^9/L
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Platelet count >50 × 10^9/L
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Calculated creatinine clearance (using the Schwartz method): during study Stage 1, >80 mL/min/1.73m2 and during study Stage 2, >60 mL/min/1.73m2
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Aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase(SGOT), alanine aminotransferase(ALT)/serum glutamic pyruvic transaminase (SGPT) and total bilirubin <3 × upper limit of normal
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The patient and/or their parent/legal guardian is willing and able to provide signed informed consent
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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:
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Any form of leukemia
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A co-morbid condition which, in the view of the Investigator, renders the patient at high-risk from treatment complications
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Previous stem cell transplantation
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Persistent high percentage marrow involvement prior to mobilization will be prohibited.
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On-going toxicities (excluding alopecia) Grade ≥2 resulting from prior chemotherapy
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Acute infection
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Fever (temperature >38.5°C) - if fever is between 37°C and 38.5°C, infection must be excluded as a cause
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Known HIV seropositivity, AIDS, hepatitis C or active hepatitis B infections
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Positive pregnancy test in post pubertal girls
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History of clinically significant cardiac abnormality or arrhythmia
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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
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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 | |
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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.- DFI12860
- 2010-019340-40
- MOZ15609