Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia (HEMOS AML 0106)
13 augusti 2009 uppdaterad 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and 35% of over 250 patient samples ( data generated in collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our Institute and University of Modena,Italy)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.
Studieöversikt
Status
Okänd
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Förväntat)
72
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Bologna, Italien, 40138
- Rekrytering
- Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-Malpighi
-
Kontakt:
- Giovanni Martinelli, MD
- Telefonnummer: +039 051 6363829
- E-post: martg@tin.it
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
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)
Tidsram: August 2007
|
August 2007
|
|
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)
Tidsram: December 2008
|
December 2008
|
|
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.
Tidsram: June 2010
|
June 2010
|
Sekundära resultatmått
Resultatmått |
|---|
|
To investigate the effect of Velcade on the expression of NFkB, and biomarkers of NFkB
|
|
Including phosphorylation of c-Rel on leukaemic blasts by flow cytometry, protein analysis,
|
|
Immunohistochemistry, and/or mRNA profiling using gene and SNPs DNA chip.
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Giovanni Martinelli, MD, Istituto di Ematologia ed Oncologia Medica "L.eA.Seràgnoli" Policlinico S.Orsola-Malpighi di Bologna
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 mars 2007
Primärt slutförande
7 december 2022
Avslutad studie
7 december 2022
Studieregistreringsdatum
Först inskickad
2 augusti 2007
Först inskickad som uppfyllde QC-kriterierna
2 augusti 2007
Första postat (Uppskatta)
3 augusti 2007
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
14 augusti 2009
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
13 augusti 2009
Senast verifierad
1 augusti 2009
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- HEMOS AML 0106
- EudraCT 2007-000273-35
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
produkt tillverkad i och exporterad från U.S.A.
Nej
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .