- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT00064233
BMS-354825 in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Is Resistant to Imatinib Mesylate
A Phase I Dose-Escalation Study To Determine The Safety, Pharmacokinetics, And Pharmacodynamics Of BMS-354825 In The Treatment Of Patients With Chronic Phase Chronic Myelogenous Leukemia Who Have Hematologic Resistance To Imatinib Mesylate (Gleevec
RATIONALE: BMS-354825 may stop the growth of cancer cells by stopping the enzymes necessary for cancer cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of BMS-354825 in treating patients with chronic phase chronic myelogenous leukemia that is resistant to imatinib mesylate.
A tanulmány áttekintése
Részletes leírás
OBJECTIVES:
- Determine the maximum tolerated dose, maximum administered dose, dose-limiting toxicity, and a recommended phase II dose of BMS-354825 in patients with chronic phase chronic myelogenous leukemia who have hematologic resistance to imatinib mesylate.
- Determine the safety and tolerability of this drug in these patients.
- Determine the plasma pharmacokinetics of this drug in these patients.
- Determine, preliminarily, the efficacy of this drug, in terms of hematologic, cytogenetic, and molecular responses in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive oral BMS-354825 once daily on days 1-5. Courses repeat every 7 days for at least 3 months in the absence of disease progression or unacceptable toxicity. Patients may receive further treatment in the absence of disease progression.
Cohorts of 3-6 patients receive escalating doses of BMS-354825 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Once the MTD is determined, 20 additional patients receive treatment as in phase I at the MTD of BMS-354825.
Patients are followed for at least 30 days.
PROJECTED ACCRUAL: Approximately 50 patients (30 for phase I and 20 for phase II) will be accrued for this study within 12-18 months.
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 1. fázis
Kapcsolatok és helyek
Tanulmányi helyek
-
-
California
-
Los Angeles, California, Egyesült Államok, 90095-1781
- Jonsson Comprehensive Cancer Center at UCLA
-
-
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
INCLUSION CRITERIA:
- Diagnosis of Philadelphia chromosome positive, chronic phase chronic myelogenous leukemia (CML) meeting all of the following criteria*:
- Less than 15% blasts in peripheral blood and bone marrow
- Less than 20% basophils in peripheral blood
- Less than 30% blasts and promyelocytes in peripheral blood and bone marrow
- Platelet count at least 100,000/mm^3 NOTE: *Patients who previously met the criteria for accelerated phase or blast phase CML, responded to treatment, and currently meet the criteria for chronic phase CML are eligible
- Primary or acquired hematologic resistance to imatinib mesylate OR intolerance to imatinib mesylate defined as follows:
Primary hematologic resistance is defined as failure to reach complete hematologic response (CHR) with a dose of 400 mg/day continued for at least 3 months
- Patients with hematological progression (i.e., WBC at least 10,000/mm^3 and rising consistently on at least 2 consecutive measurements obtained at least 14 days apart) while receiving imatinib mesylate of 400 mg/day are eligible if they have received less than 3 months of therapy
Acquired hematologic resistance is defined as achieving a CHR, but subsequently developing a rising WBC to at least 10,000/mm^3
- WBC must be at least 10,000/mm^3 and rising on at least 2 measurements obtained at least 14 days apart with at least 1 of these measurements greater than 15,000/mm^3
Intolerance is defined as having discontinued imatinib mesylate due to nonhematologic toxicity of any grade
- CD4^+ T-cell count at least 350/mm^3
- 18 and over
- ECOG 0-1
- Life expectancy, At least 6 months.
Hepatic
- Bilirubin no greater than 1.5 mg/dL
- ALT and AST no greater than 2.0 times upper limit of normal (ULN)
Renal
- Creatinine no greater than 1.5 times ULN
- Potassium normal*
- Magnesium normal*
- Serum calcium or ionized calcium at least lower limit of normal NOTE: *Patients with low levels may be repleted to be eligible
- Negative pregnancy test
- Fertile patients must use effective contraception for 1 month before, during, and 1 month after study participation
- More than 14 days since prior interferon
- More than 14 days since prior cytarabine
- More than 3 days since prior hydroxyurea
- More than 28 days since other prior investigational or antineoplastic agents
- More than 7 days since prior imatinib mesylate
- At least 5 days or 5 half-lives since prior medications that inhibit platelet function, including the following:
- Aspirin
- Dipyridamole
- Epoprostenol
- Eptifibatide
- Clopidogrel
- Cilostazol
- Abciximab
- Ticlopidine
- At least 5 days or 5 half-lives since prior anticoagulants such as warfarin or heparin/low molecular weight heparin (e.g., danaparoid, dalteparin, tinzaparin, enoxaparin)
- At least 5 days or 5 half-lives since prior drugs accepted to have a risk of causing torsades de pointes, including the following:
- Class IA antiarrhythmic agents (e.g., quinidine, procainamide, or disopyramide)
- Class III antiarrhythmic agents (e.g., amiodarone, sotalol, ibutilide, or dofetilide)
- Macrolide antibiotics (e.g., erythromycin or clarithromycin)
- Antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, or pimozide)
- Tricyclic antidepressants
- Cisapride
- Bepridil
- Inapsine
- Methadone
- Arsenic
- Concurrent anagrelide for thrombocytosis due to CML allowed
Exclusion Criteria:
- extramedullary involvement (other than liver or spleen)
- significant bleeding disorder unrelated to CML
- acquired bleeding disorder within the past year (e.g., acquired antifactor VIII antibodies)
- congenital bleeding disorders (e.g., von Willebrand disease)
- uncontrolled or significant cardiovascular disease
- uncontrolled angina within the past 6 months
- congestive heart failure within the past 6 months
- myocardial infarction within the past 12 months
- history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
- history of second or third degree heart block (may be eligible if patient has a pacemaker)
- diagnosed or suspected congenital long QT syndrome
- prolonged QTc interval on pre-entry EKG (i.e., greater than 450 msec)
- heart rate less than 50/minute on pre-entry EKG
- uncontrolled hypertension
- vasculitis
- pregnant or nursing
- gastrointestinal tract bleeding within the past 6 months
- connective tissue disorders
- other serious uncontrolled medical disorder or active infection that would impair the ability to receive study therapy
- dementia or altered mental status that would preclude giving informed consent
- evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, EKG, or clinical laboratory determinations unrelated to CML
- prisoners or patients who are compulsorily detained (e.g., involuntary incarceration for treatment of either a psychiatric or physical [e.g., infectious disease] illness)
- concurrent drugs accepted to have a risk of causing torsades de pointes
- other concurrent treatment for CML
- concurrent dolasetron or droperidol
- concurrent anticoagulants
- concurrent medications that inhibit platelet function
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Maszkolás: Nincs (Open Label)
Együttműködők és nyomozók
Szponzor
Együttműködők
Nyomozók
- Kutatásvezető: Charles Sawyers, MD, Jonsson Comprehensive Cancer Center
Publikációk és hasznos linkek
Általános kiadványok
- Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O'Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006 Jun 15;354(24):2531-41. doi: 10.1056/NEJMoa055229.
- Cortes J, Sawyers CL, Kantarjian HM, et al.: Long-term efficacy of dasatinib in chronic-phase CML: results from the phase I trial (CA180002). [Abstract] Blood 110 (11): A-1026, 2007.
- Talpaz M, Kantarjian HM, Paquette R, et al.: A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant chronic phase chronic myeloid leukemia (CML): results from CA180002. [Abstract] J Clin Oncol 23 (Suppl 16): A-6519, 564s, 2005.
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Becslés)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
- Neoplazmák szövettani típus szerint
- Neoplazmák
- Csontvelő-betegségek
- Hematológiai betegségek
- Mieloproliferatív rendellenességek
- Leukémia
- Leukémia, mieloid
- Leukémia, mielogén, krónikus, BCR-ABL pozitív
- Leukémia, mieloid, krónikus fázis
- A farmakológiai hatás molekuláris mechanizmusai
- Enzim gátlók
- Antineoplasztikus szerek
- Protein kináz inhibitorok
- Dazatinib
Egyéb vizsgálati azonosító számok
- CDR0000310142
- UCLA-0303035
- BMS-CA180002
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .
Klinikai vizsgálatok a dasatinib
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Befejezve
-
Hyoung Jin KangMég nincs toborzásAkut limfoblasztikus leukémia, gyermekgyógyászat
-
Xspray Pharma ABQPS Bioserve India Pvt LimitedBefejezve
-
Bristol-Myers SquibbBefejezveFarmakokinetikai vizsgálat egészséges résztvevők körébenEgyesült Államok
-
Baylor College of MedicineToborzásKrónikus mieloid leukémia | Krónikus mieloid leukémia, BCR/ABL-pozitív, remisszióban | Krónikus mieloid leukémia remisszióbanEgyesült Államok
-
University of Massachusetts, WorcesterBristol-Myers SquibbMegszűntKrónikus mielogén leukémiaEgyesült Államok
-
Peking University Cancer Hospital & InstituteIsmeretlenGasztrointesztinális stroma tumorKína
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)Befejezve
-
Kanto CML Study GroupIsmeretlenMielogén leukémia, krónikus, krónikus fázisJapán
-
Swiss Group for Clinical Cancer ResearchBefejezveGasztrointesztinális stroma tumorFranciaország, Svájc, Németország, Finnország