Hemotrial Un proyecto de SEHH

Ensayo clínico

A Randomized Two-Arm, Multicenter, Open-Label Phase II Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects with Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia who are Resistant or Intolerant to Imatinib Mesylate (Gleevec)

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A Randomized Two-Arm, Multicenter, Open-Label Phase II Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects with Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia who are Resistant or Intolerant to Imatinib Mesylate (Gleevec)


Resumen

2017-03-15 03:56:59
2005-001169-32
CA180-035
A Randomized Two-Arm, Multicenter, Open-Label Phase II Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects with Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia who are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
CA180-035

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 Myeloid Leukemia (CML) in Accelerated Phase (AP) or in Myeloid (My) or Lymphoid (Ly) Blast Phase (BP) or with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) who are Resistant or Intolerant to Imatinib Mesylat


The primary objective is to estimate the rate of CHR for both schedules (70 mg BID and 140 mg QD) separately in subjects with AP CML or MyBP CML or LyBP CML and Ph+ ALL who have primary or acquired resistance to imatinib mesylate.

In imatinib-resistant subjects by arm:1) To estimate the rate of OHR and CyR 2) To assess the time to, and duration of CHR and OHR 3) To assess progression-free and overall survival 4) To estimate the difference between arms, of CHR and OHR ratesIn imatinib-intolerant subjects by arm:5) To estimate the rates of CHR, OHR and CyR In all subjects by arm:6) To assess the safety of BMS-354825, in particular the incidence of major adverse events, the number of dose interruptions, dose reductions and treatment discontinuation for toxicity7) To collect pharmacokinetics data 8) To describe the spectrum of mutations at baseline and at time of PD and to explore the roles of BCR-ABL mRNA point mutations in the BCR-ABL gene as predictors or surrogates of response 9) To collect Health Utility data using the EuroQoL (EQ-5D)

Information no disponible en EudraCT


1/ AP CMLSubjects with Ph+ (or BCR/ABL+) AP CML whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate.Subjects are considered to have AP CML if they meet at least one of the following criteria:• At least 15% to < 30% blasts in PB or in BM• A sum of the percent of blasts and promyelocytes in PB or the BM ? 30% (with < 30% blasts alone)• ? 20% basophils in PB or BM•Platelets < 100,000/mm³ unrelated to prior drug therapySubjects may not have extra-medullar infiltrates of leukemic cells other than in spleen or liver.In addition, the following subjects will be considered to be part of the AP CML population even if they do not reach the above defined values of blast % in PB or BM for accelerated phase:• Subjects with clonal evolution (e.g. +8, +19, +Ph, iso17)• Subjects with prior episode of AP who achieved a hematologic response and subsequently progressed 2/ BP CMLSubjects with Ph+ (or BCR/ABL+) MyBP or LyBP CML whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate.Subjects are considered to have myeloid or lymphoid BP CML if they meet at least one of the following criteria:• ? 30% myeloid or lymphoid blasts in PB or in BM • Extra-medullar infiltrates of leukemic cells, other than in spleen or liver, with myeloid or lymphoid blast morphologySubjects with prior episode of BP who achieved a hematologic response and subsequently progressed but do not meet the criteria for BP CML as described above will be considered to be part of the BP CML population.3/ Ph+ ALL Subjects with Ph+ (or BCR/ABL+) ALL whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate. Subjects must have received at least one prior standard induction +/- consolidation chemotherapy regimen and not be eligible for immediate autologous or allogeneic stem cell transplantation.Subjects with CNS involvement must have received intra-thecal chemotherapy and obtain normal CSF for at least 2 weeks prior to entry. Maintenance intra-thecal chemotherapy must be given during treatment with BMS-354825.Subjects characterisctics:4) ECOG performance status (PS) score 0 - 2 (See Protocol Appendix 1) 5) 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 ULN6) Adequate renal function defined as:• serum creatinine ? 1.5 times the institutional ULN7) Serum Na, K, Mg, P and total serum Ca or ionized Ca levels must be greater than or 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.8) Men and women, ages 18 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 least 3 months after completion of the study medication.3. Women with a positive pregnancy test on enrollment or prior to study drug administration.4. Subjects eligible for immediate autologous or allogeneic stem cell transplantation.5. Subjects with active CNS involvement (presence of leukemic cells in the CSF)6. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy7. Uncontrolled or significant cardiovascular disease (see Protocol section 5.2 for details)8. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent9. History of significant bleeding disorder unrelated to CML (see Protocol section 5.2 for details)10. Concurrent incurable malignancy other than CML11. Evidence of organ dysfunction or digestive dysfunction that would prevent administration 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 including BMS-354825• any other investigational or any antineoplastic agent other than hydroxyurea (HU) within 2 days 13. Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointe (see Protocol section 5.2 for details)14. Subjects taking medications that irreversibly inhibit platelet function or anticoagulants 15. Prior therapy with BMS-354825

EfficacyThe primary efficacy endpoint is the rate of CHR. The secondary efficacy endpoints include the rates of overall hematologic response (OHR) and cytogenetic response (CyR), the difference of CHR between arms, the difference of OHR between arms, time to, and duration of CHR and OHR, progression-free and overall survival.Health Utility measurement will be done. The spectrum of mutations at baseline and at time of progressive disease will be described.Safety/ToxicityToxic effects will be assessed continuously. Safety and tolerability of BMS-354825 will be reported for all treated subjects. Adverse events and other symptoms will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All subjects will be followed until death.Subjects will also participate in the collection of population pharmacokinetics data.

Fase II
  DISEÑO DEL ENSAYO:

No
Si

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT
  COMPARADOR DEL ENSAYO CONTROLADO:

No
No

No
No

Si

Centros participantes:


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


8
  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:


145
264

Investigadores

  INVESTIGADORES QUE PARTICIPAN EN EL ESTUDIO

Estado actual


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En Marcha