Hemotrial Un proyecto de SEHH

Ensayo clínico

A Randomized Two-by-Two, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 50 mg or 70 mg Twice Daily or 100 mg or 140 mg Once Daily in Subjects with Chronic Phase Philadelphia Chromosome or BCR-ABL Positive Chronic Myelogenous Leukemia Who are Resistant or Intolerant to Imatinib Mesylate (Gleevec®)Revised Protocol 01 version 3.0, incorporating Administrative Letter 01

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Resumen

2017-03-15 03:57:03
2005-001294-99
CA180-034
A Randomized Two-by-Two, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 50 mg or 70 mg Twice Daily or 100 mg or 140 mg Once Daily in Subjects with Chronic Phase Philadelphia Chromosome or BCR-ABL Positive Chronic Myelogenous Leukemia Who are Resistant or Intolerant to Imatinib Mesylate (Gleevec®)Revised Protocol 01 version 3.0, incorporating Administrative Letter 01
CA180-034

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
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

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 2:
Test
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

Information no disponible en EudraCT
Information no disponible en EudraCT

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 Chronic Phase Philadelphia Chromosome or BCR-ABL Positive Chronic Myelogenous Leukemia who are resistant or intolerant to Imatinib Mesylate

To compare the efficacy of BMS-354825 as defined by MCyR when administered QD relative to BMS-354825 administered BID in the treatment of CP CML imatinib-resistant subjects.The QD schedule will be considered efficacious if it can be demonstrated that the true MCyR rate is no more than 15% less than that of the BID schedule.

The main secondary objective is to estimate the difference of MCyR rates between the two TDD levels (MCyRR100 mg TDD minus MCyRR140 mg TDD) in the imatinib-resistant subjects.Other secondary objectives are:1) In the imatinib-resistant subjects, by TDD, schedule and arm• To estimate the rate of MCyR and CHR• To estimate the time to, and duration of MCyR and CHR• To evaluate PFS and OS2) In the imatinib-intolerant subjects• To assess efficacy (MCyR and CHR)3) In all treated subjects• To assess the safety of BMS-354825 by TDD, schedule and arm• To compare the rates of specific adverse events (e.g. fluid retention, pleural/pericardial effusion, myelosuppression, and dose reduction due to toxicity)between the two schedules and two TDD• To collect PK data and Heath Utility measurements by arm• To describe the spectrum of mutation and to explore the level of expression of theBCR-ABL gene

Information no disponible en EudraCT


1) Subjects with a myeloproliferative disorder defined as Ph+ (or BCR/ABL+) CP CML whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate are eligible. Subjects can be pretreated with IFN, standard chemotherapy or high-dose chemotherapy and stem-cell transplantation.Subjects considered to have Ph+ (or BCR/ABL+) CP CML must meet all the followingcriteria:• < 15% blasts in PB cells or BM• < 30% blasts + promyelocytes in PB cells or BM• < 20% basophils in PB cells• Platelets ? 100,000/mm³ (or less if related to prior drug therapy)• No extra-medullar involvement (except liver or spleen)Subjects with previous history of AP or BP CML and subjects with clonal evolution are not eligible even if they still meet the criteria for CP as defined above. They are considered in cytogenetic AP.2) ECOG performance status (PS) score 0 - 2 (See Protocol Appendix 1)3) Adequate hepatic function defined as:• total bilirubin ? 2.0 times the institutional ULN• alanine aminotransferase (ALT) and aspartate aminotransferase (AST)? 2.5 times the institutional ULN4) Adequate renal function defined as:• serum creatinine ? 1.5 times the institutional ULN5) Serum Na, K, Mg, P and total serum Ca or ionized Ca levels must be greater thanor equal to the institutional lower limit of normal. Subjects with low K, Mg levels,total serum Ca and/or ionized Ca must be repleted to allow for protocol entry.6) Men and women, 18 years of age and older

1) Women who are pregnant or breastfeeding2) 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 least3 months after completion of the study medication.3) Women with a positive pregnancy test on enrollment or prior to study drugadministration.4) Subjects eligible for immediate autologous or allogeneic stem cell transplantation.5) A serious uncontrolled medical disorder or active infection that would impair theability of the subject to receive protocol therapy6) Uncontrolled or significant cardiovascular disease (see Protocol section 5.2 for details)7) History of significant bleeding disorder unrelated to CML8) Clinically significant bleeding from the GI tract within 6 months9) Concurrent incurable malignancy other than CML10) Dementia or altered mental status that would prohibit the understanding or rendering of informed consent11) Evidence of organ dysfunction or digestive dysfunction that would preventadministration of study therapy12) Subjects who received any of the following:• imatinib mesylate within 7 days• interferon or cytarabine within 7 days• a targeted small molecule anti-cancer agent within 7 days• any other investigational or any antineoplastic agent other than hydroxyurea (HU)within 28 days13) Subjects currently taking the following drugs that are generally accepted to have a risk of causing Torsades de Pointe (see Protocol section 5.2 for details)14) Subjects who have discontinued any of these medications must have a wash-outperiod of at least 5 days or at least 5 half-lives of the drug (whichever is greater) prior to the first dose of BMS-354825.15) Subjects taking medications that irreversibly inhibit platelet function or anticoagulants

Efficacy:The primary efficacy endpoint is the rate of MCyR.Secondary efficacy endpoints include the rate of CHR, time to, and duration of MCyR and CHR, PFS and OS.Definitions of response and progression are detailed in Section 3.3 of the Protocol.Safety/Toxicity:Toxic effects will be assessed continuously. Safety and tolerability of BMS-354825 will be reported for all randomized subjects. Adverse events and other symptoms will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.Other Endpoints:Additional secondary endpoints include the collection of pharmacokinetics (PK) data and Health Utility measurements, and the exploration of the spectrum of BCR-ABL mutations and of the level of expression of the BCR-ABL gene.

Fase III
  DISEÑO DEL ENSAYO:

Si
Si

Si
No

No
Si

No
Si
  COMPARADOR DEL ENSAYO CONTROLADO:

No
No

No
No

Si

Centros participantes:

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


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:

9

Para estudios internacionales:

236
400

Investigadores

  INVESTIGADORES QUE PARTICIPAN EN EL ESTUDIO

Estado actual


 EC Finalizado



EC Finalizado