Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia (HEMOS AML 0106)
13. august 2009 oppdatert av: University of Bologna
Phase II, Open-Label, Multi-centre, 2-part Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Unfit for Conventional Chemotherapy ( >18 Years) or in Patients With Acute Myeloid Leukemia in First Relapse ( >60 Years)
This is one of the first studies of combination of Zarnestra plus Velcade in man. A primary objective of the study is therefore to assess the safety and tolerability of multiple doses of Zarnestra plus Velcade in patients with AML.
New treatments for patients that are untreatable with intensive chemotherapy aged de novo AML patients or post-relapse AML are urgently required since, at present, many of the drugs used for second line therapy are the same as those used for first induction and response rates are much lower.
- The following evidence suggests that Velcade plus Zarnestra can be an attractive therapeutic combination for: AML patients.
- Affymetrix gene profiling data showed expression of NFkB1 in all of 5 myeloid cell lines cell lines tested and 35% of over 250 patient samples ( data generated in collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our Institute and University of Modena,Italy)
- Preclinical evidence showed that AML cells in suspension culture were prevented to develop de novo drug resistance and mediated drug resistance.
In Part B additional patients with AML will be treated to further characterize the tolerability,biological effects, and clinical efficacy of the combination Velcade plus Zarnestra. Patients on treatment for AML will undergo regular bone marrow aspirates and biopsies to assess responses to treatment. This will facilitate frequent assessment of biological endpoints (reduction in expression and phosphorylation of IKKb kinase, and downstream markers of signalling along with apoptosis, survival, proliferation and cellular size and ploidy) will be made in an attempt to confirm that the desired biological activity has been achieved at the maximum tolerated dose.
Studieoversikt
Status
Ukjent
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Forventet)
72
Fase
- Fase 2
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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Bologna, Italia, 40138
- Rekruttering
- Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-Malpighi
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Ta kontakt med:
- Giovanni Martinelli, MD
- Telefonnummer: +039 051 6363829
- E-post: martg@tin.it
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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
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Provision of written informed consent
- Male or female aged >18 years with newly diagnosed Acute Myeloid Leukemia (AML), de novo or secondary, unfit for conventional chemotherapy
- Male or female with Acute Myeloid Leukemia in first relapse ( > 60 years)
- WHO performance status ³ 2, or/and unwillingness to receive conventional chemotherapy
- Negative pregnancy test or evidence of post-menopausal status for female patients.
- RASGRP1/APTX gene expression ratio calculated at the screening >10 (part B.2 only)
Exclusion Criteria:
- Serum bilirubin 2 x> Upper Limit of Normal (ULN)
- Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.5 x ULN
- Serum creatinine ³ 2.5 x ULN or 24-hour creatinine clearance £ 60 mL/min (measured or calculated by Cockcroft-Gault)
- Patients with AML of FAB M3 classification (APL)
- Patients with a history of another primary malignancy within the previous 1 year other than basal cell carcinoma or carcinoma in situ, the patient is in remission
- Any clinically defined central nervous system AML.
- Participation in an investigational drug study within the 30 days prior to entry
- Evidence of uncontrolled infection or CNS-Hemorrhagic
- Patients with documented cases of human immunodeficiency virus (HIV)
- Peripheral Neuropathy or Neuropathic Pain grade > or = 2
- Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
- Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 7,NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
- RASGRP1/APTX gene expression ratio calculated at the screening <10 (part B.2 only)
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: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
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PART A: Assess the safety and tolerability of combined use of Zarnestra plus multiple ascending doses of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in first or subsequent relapse ( >60 years).(COMPLETED)
Tidsramme: August 2007
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August 2007
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Part B.1: Assess the effect of Tipifarnib plus the defined in part A dose of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in Patients in first or subsequent relapse ( >60 years) (COMPLETED)
Tidsramme: December 2008
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December 2008
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Part B.2: Evaluate the overall response (CR, PR, HI) of patients with a RASGRP1/APTX gene expression ratio > 10, identified as predictive of a good clinical response to tipifarnib in patients with de novo AML unfit for conventional chemotherapy.
Tidsramme: June 2010
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June 2010
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Sekundære resultatmål
Resultatmål |
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To investigate the effect of Velcade on the expression of NFkB, and biomarkers of NFkB
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Including phosphorylation of c-Rel on leukaemic blasts by flow cytometry, protein analysis,
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Immunohistochemistry, and/or mRNA profiling using gene and SNPs DNA chip.
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Giovanni Martinelli, MD, Istituto di Ematologia ed Oncologia Medica "L.eA.Seràgnoli" Policlinico S.Orsola-Malpighi di Bologna
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
1. mars 2007
Primær fullføring
7. desember 2022
Studiet fullført
7. desember 2022
Datoer for studieregistrering
Først innsendt
2. august 2007
Først innsendt som oppfylte QC-kriteriene
2. august 2007
Først lagt ut (Anslag)
3. august 2007
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
14. august 2009
Siste oppdatering sendt inn som oppfylte QC-kriteriene
13. august 2009
Sist bekreftet
1. august 2009
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- HEMOS AML 0106
- EudraCT 2007-000273-35
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
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