A Combined Study in Pediatric Cancer Patients for Dose Ranging and Efficacy/Safety of Plerixafor Plus Standard Regimens for Mobilization Versus Standard Regimens Alone
15. mai 2017 oppdatert av: Genzyme, a Sanofi Company
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.
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.
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
46
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Gent, Belgia, 9000
- Investigational Site Number 51
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København Ø, Danmark, 2100
- Investigational Site Number 61
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Lyon, Frankrike, 69373
- Investigational Site Number 42
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Paris Cedex 05, Frankrike, 75248
- Investigational Site Number 43
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Petach Tikva, Israel, 4920235
- Investigational Site Number 92
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Tel-Aviv, Israel, 64239
- Investigational Site Number 91
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Genova, Italia, 16100
- Investigational Site Number 21
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Milano, Italia, 20133
- Investigational Site Number 24
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Padova, Italia, 35128
- Investigational Site Number 23
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Roma, Italia, 00165
- Investigational Site Number 22
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Torino, Italia, 10126
- Investigational Site Number 26
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Amsterdam, Nederland, 1105 AZ
- Investigational Site Number 72
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Rotterdam, Nederland, 3015 GJ
- Investigational Site Number 71
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Krakow, Polen, 30-663
- Investigational Site Number 85
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Wroclaw, Polen, 50-368
- Investigational Site Number 84
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Barcelona, Spania, 08035
- Investigational Site Number 94
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Madrid, Spania, 28009
- Investigational Site Number 93
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Birmingham, Storbritannia, B4 6NH
- Investigational Site Number 11
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Glasgow, Storbritannia, G51 4TF
- Investigational Site Number 13
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Brno, Tsjekkia, 62500
- Investigational Site Number 81
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Praha 5 - Motol, Tsjekkia, 15006
- Investigational Site Number 82
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Frankfurt Am Main, Tyskland, 60590
- Investigational Site Number 33
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Freiburg, Tyskland, 79106
- Investigational Site Number 34
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Hamburg, Tyskland, 20246
- Investigational Site Number 35
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Hannover, Tyskland, 30625
- Investigational Site Number 31
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München, Tyskland, 80337
- Investigational Site Number 36
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Budapest, Ungarn, 1097
- Investigational Site Number 83
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
1 år til 18 år (Barn, Voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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).
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160 μg/kg subcutaneous (SC) injection
240 μg/kg subcutaneous (SC) injection
320 μg/kg subcutaneous (SC) injection
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Eksperimentell: 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).
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160 μg/kg subcutaneous (SC) injection
240 μg/kg subcutaneous (SC) injection
320 μg/kg subcutaneous (SC) injection
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Eksperimentell: 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).
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160 μg/kg subcutaneous (SC) injection
240 μg/kg subcutaneous (SC) injection
320 μg/kg subcutaneous (SC) injection
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
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Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2
Tidsramme: Up to 5 days
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Up to 5 days
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg
Tidsramme: Up to 5 days
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During Stage 1 and Stage 2
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Up to 5 days
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Yield of CD34+ cells for each apheresis
Tidsramme: Up to 5 days
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During Stage 1 and Stage 2
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Up to 5 days
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Total CD34+ cell yield
Tidsramme: Up to 5 days
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During Stage 1 and Stage 2
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Up to 5 days
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Percentage of patients proceeding to transplant
Tidsramme: Within 6 months of last apheresis
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During Stage 1 and Stage 2
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Within 6 months of last apheresis
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Percentage of patients successfully engrafting
Tidsramme: 3, 6, 12 and 24 months post-transplant
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During Stage 1 and Stage 2
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3, 6, 12 and 24 months post-transplant
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Percentage of patients with durable engraftment
Tidsramme: 3, 6, 12 and 24 months post-transplant
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During Stage 1 and Stage 2
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3, 6, 12 and 24 months post-transplant
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Summary of adverse events (AEs)
Tidsramme: 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)
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During Stage 1 and Stage 2
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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)
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Duration of hospitalizations (planned or unplanned)
Tidsramme: Throughout the duration of the study
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During Stage 1 and Stage 2
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Throughout the duration of the study
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Mobilization of tumor cells into peripheral blood
Tidsramme: Up to 5 days
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During Stage 1 and Stage 2
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Up to 5 days
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Relapse rates
Tidsramme: 3, 6, 12 and 24 months post-transplant
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During Stage 1 and Stage 2
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3, 6, 12 and 24 months post-transplant
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Occurrence of secondary malignancies
Tidsramme: 3, 6, 12 and 24 months post-transplant
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During Stage 1 and Stage 2
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3, 6, 12 and 24 months post-transplant
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Incidence of primary and secondary graft failure
Tidsramme: 3, 6, 12 and 24 months post-transplant
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During Stage 1 and Stage 2
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3, 6, 12 and 24 months post-transplant
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Time to secondary graft failure
Tidsramme: Up to 24 months post-transplant
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During Stage 1 and Stage 2
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Up to 24 months post-transplant
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Survival rates
Tidsramme: 3, 6, 12 and 24 months post-transplant
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During Stage 1 and Stage 2
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3, 6, 12 and 24 months post-transplant
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Sebastien B, Cheverton P, Magnin C, Aouni J, Castan R. Development and validation of a predictive model to guide the use of plerixafor in pediatric population. Bone Marrow Transplant. 2022 Dec;57(12):1827-1832. doi: 10.1038/s41409-022-01831-2. Epub 2022 Sep 26.
- Morland B, Kepak T, Dallorso S, Sevilla J, Murphy D, Luksch R, Yaniv I, Bader P, Rossler J, Bisogno G, Maecker-Kolhoff B, Lang P, Zwaan CM, Sumerauer D, Krivan G, Bernard J, Liu Q, Doyle E, Locatelli F. Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC). Bone Marrow Transplant. 2020 Sep;55(9):1744-1753. doi: 10.1038/s41409-020-0836-2. Epub 2020 Mar 3.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
3. mars 2014
Primær fullføring (Faktiske)
9. mai 2017
Studiet fullført (Faktiske)
9. mai 2017
Datoer for studieregistrering
Først innsendt
28. januar 2011
Først innsendt som oppfylte QC-kriteriene
1. februar 2011
Først lagt ut (Anslag)
2. februar 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
16. mai 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
15. mai 2017
Sist bekreftet
1. mai 2017
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Neoplasmer, bindevev og mykt vev
- Neoplasmer etter histologisk type
- Neoplasmer
- Neoplasmer, kjertel og epitel
- Neoplasmer, Neuroepithelial
- Nevroektodermale svulster
- Neoplasmer, kjønnsceller og embryonale
- Neoplasmer, nervevev
- Osteosarkom
- Neoplasmer, beinvev
- Neoplasmer, bindevev
- Neuroektodermale svulster, primitive
- Neuroektodermale svulster, primitive, perifere
- Sarkom
- Sarkom, Ewing
- Nevroblastom
- Anti-infeksjonsmidler
- Antivirale midler
- Anti-HIV-midler
- Antiretrovirale midler
- Plerixafor
Andre studie-ID-numre
- DFI12860
- 2010-019340-40 (EudraCT-nummer)
- MOZ15609 (Annen identifikator: Genzyme other study code)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .