Hemotrial Un proyecto de SEHH

Ensayo clínico

An open-label, randomized study of dasatinib vs. high-dose (800 mg) imatinib in the treatment of subjects with chronic phase chronic myeloid leukemia who have had a suboptimal response after at least 3 months of therapy with 400 mg imatinib.Estudio aleatorizado, abierto, de dasatinib frente a imatinib, a dosis altas (800 mg), en el tratamiento de sujetos con leucemia mieloide crónica, en fase crónica, con respuesta subóptima a imatinib 400 mg después de, al menos, 3 meses de tratamiento.Revised Protocol 02, incorporating Administrative Letter 01 and Protocol Amendments 02 (Version 1.0, Dated 29-May-2007) & 3 (Version 1.0, Dated 10-Oct-2007).

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Resumen

2017-03-15 03:58:22
2005-005153-22
CA180-043
An open-label, randomized study of dasatinib vs. high-dose (800 mg) imatinib in the treatment of subjects with chronic phase chronic myeloid leukemia who have had a suboptimal response after at least 3 months of therapy with 400 mg imatinib.Estudio aleatorizado, abierto, de dasatinib frente a imatinib, a dosis altas (800 mg), en el tratamiento de sujetos con leucemia mieloide crónica, en fase crónica, con respuesta subóptima a imatinib 400 mg después de, al menos, 3 meses de tratamiento.Revised Protocol 02, incorporating Administrative Letter 01 and Protocol Amendments 02 (Version 1.0, Dated 29-May-2007) & 3 (Version 1.0, Dated 10-Oct-2007).
CA180-043

PROMOTORES DEL ENSAYO
Nombre del promotor Organización Persona de contacto País
Bristol-Myers Squibb International Corporation Belgium

Fármacos

  INFORMACIÓN DE FÁRMACOS USADOS:
  FÁRMACO 1:
Test Sprycel
Bristol-Myers Squibb Pharma EEIG BMS-354825-03
BMS-354825-03 Tablet
Oral use

Detalles del Fármaco (Principio Activo):

BMS-354825-03

Concentración del fármaco:

mg milligram(s) equal

20

Contenido del fármaco


Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 2:
Test Sprycel
Bristol-Myers Squibb Pharma EEIG BMS-354825-03
BMS-354825-03 Tablet
Oral use

Detalles del Fármaco (Principio Activo):

BMS-354825-03

Concentración del fármaco:

mg milligram(s) equal

50

Contenido del fármaco


Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 3:
Comparator Gleevec
Novartis Gleevec
Tablet
Oral use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:

mg milligram(s) equal

100

Contenido del fármaco


Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 4:
Comparator Gleevec
Novartis Gleevec
Tablet
Oral use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:

mg milligram(s) equal

400

Contenido del fármaco


Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  INFORMACIÓN DE PLACEBOS USADOS:

No hay placebos asignados al ensayo

Información General



Sindromes Mieloproliferativos

Subjects with Ph+ chronic phase Chronic Myeloid leukemia (CML).Sujetos con Leucemia Mieloide Crónica en fase crónica con cromosoma Philadelphia Positivo.


The primary objective of this study is to compare the rate of major molecular response of dasatinib (100 mg QD) to high-dose imatinib (800 mg, i.e. 400 mg BID) therapy at 12 months in chronic phase CML subjects, who had achieved only a suboptimal response after at least 3 months imatinib (400 mg) monotherapy prior to enrollment. A suboptimal response is defined as a hematologic response but less than Complete HR after at least 3 months; a cytogenetic response but less than a partial cytogenetic response (PCgR) after at least 6 months; a partial cytogenetic response after at least 12 months, or less than a major molecular response with complete cytogenetic response after at least 18 months.Additional 12 months of treatment:The primary objective is to collect longer term efficacy on dasatinib in terms of duration of major molecular response.

• To estimate the rates of Complete Cytogenetic Response (CCgR) at months 6 and 12 in both treatment arms• To estimate the time to Major Molecular Response (MMolR) and TTF, PFS in both treatment arms• To assess the safety of dasatinib and high-dose imatinib• To establish BCR/ABL kinase domain mutation rate• To investigate causes and mechanisms of resistance• To evaluate the quality of life (QOL) in each treatment armAdditional 12 months of treatment:The secondary objective is to provide access to study treatment for those patients who are benefiting from 800 mg imatinib and to obtain further safety data.

No


1) Subjects able to provide written informed consent2) Available for periodic follow up3) Life expectancy of at least approximately 3 monthsTarget population4) Subjects with Ph+ chronic phase CML who achieved only a suboptimal response (defined as a HR which is

Sex and Reproductive Status1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least one month before and for at least 3 months after completion of study medication.2) Women who are pregnant or breastfeeding3) Women with a positive pregnancy test on enrollment or prior to study drug administration.4) Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 3 months after completion of study medication.Target Disease Exceptions5) Subjects eligible for immediate autologous or allogeneic stem cell transplantation.6) Previous diagnosis of accelerated phase or blast crisis CML7) Subjects who have previously documented T315I mutation. Screening for mutation is not required for enrollment onto the protocol.8) Subjects with a MMolR9) Subjects with no hematologic response10) Subjects who lost previously documented CHR, PCgR or CCgRMedical History and Concurrent Diseases11) A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy12) Uncontrolled or significant cardiovascular disease, including:a) A myocardial infarction within 6 monthsb) Uncontrolled angina within 3 monthsc) Congestive heart failure within 3 monthsd) Diagnosed or suspected congenital long QT syndromee) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe)f) Prolonged QTc interval > 500 msec on pre-entry ECG according to Fridericia formulag) Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)h) Heart rate consistently < 50 beats/minute on pre-entry ECGi) Uncontrolled hypertension13) History of significant bleeding disorder unrelated to CML, including:a) Diagnosed congenital bleeding disorders b) Diagnosed acquired bleeding disorder within one year c) Clinically significant bleeding from the GI tract within 6 months14) Concurrent other malignancies other than CMLPhysical and Laboratory Test Findings15) Intolerance to imatinib 400 mg. Intolerance is defined as occurrence of any of the following at any time during treatmenta) Imatinib-related grade 3 or greater non-hematologic toxicityb) Imatinib-related grade 4 hematologic toxicity lasting more than 7 daysc) Imatinib-related toxicity leading to imatinib discontinuation or disruption in dosing for >4 weeksProhibited Therapies and/or Medications16) Prior treatment with imatinib at a dose > 400 mg17) Less than 3 months of prior treatment with imatinib18) Time from initial diagnosis of CML to start of first imatinib dose > 6 months19) Subjects with prior stem cell transplantation and/or high dose chemotherapy for CML20) Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:- quinidine, procainamide, disopyramide- amiodarone, sotalol, ibutilide, dofetilide- erythromycins, clarithromycin- chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, zyprasidone- cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is greater) prior to the first dose of dasatinib.21) Subjects taking medications that inhibit platelet function or anticoagulants (Low-dose warfarin for prophylaxis to prevent catheter thrombosis, and heparin-flushes for IV lines is permitted);22) Prior therapy with dasatinib or other experimental agent for CMLOther Exclusion Criteria23) Prisoners or subjects who are involuntarily incarcerated. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Efficacy:• Primary endpoint: proportion of subjects achieving a MMolR rate at 12 months• Secondary endpoints: CCgR rate at 6 and 12 months, time to MMolR, TTF and PFS.Subjects who have a confirmed MMolR at 12 months on treatment will be counted as responders (if first MMolR is at month 12, the confirmed MMolR should occur at month 13). Treatment failure will be defined as failure to complete 12 months of treatment or failure to achieve a MMolR at 12 months of study treatment. Subjects who achieved a MMolR earlier than 12 months, but have lost this response at evaluation at 12 months, will not be considered responders.Safety:Safety and tolerability of dasatinib and imatinib will be reported for all randomized subjects. Adverse events will be assessed continuously and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.Mutation and resistance analysis:Mutation analysis will be performed in all subjects at baseline, at the time of progression during study treatment or after 12 months of treatment.

Fase II
  DISEÑO DEL ENSAYO:

Si
Si

Si
No

No
Si

No
No
  COMPARADOR DEL ENSAYO CONTROLADO:

Si
No

No
No

Si

Centros participantes:


Si
Information no disponible en EudraCT
  TIEMPO ESTIMADO DURACIÓN DEL ENSAYO:

2
9
  TIEMPO ESTIMADO DURACIÓN DEL ENSAYO EN ESPAÑA:


  POBLACIÓN DE PACIENTES EN EL ESTUDIO:
  Población de pacientes: 1

Rango de edad:


0
1

1

Sexo:


1
1

Número planeado de pacientes a incluir:


24

Para estudios internacionales:


135
168

Investigadores

  INVESTIGADORES QUE PARTICIPAN EN EL ESTUDIO

Estado actual


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