Hemotrial Un proyecto de SEHH

Ensayo clínico

A Phase 1/2 Study of SKI-606 in Philadelphia Chromosome Positive LeukemiasEstudio de Fase 1/2 de SKI-606 en Leucemias con Cromosoma Filadelfia Positivo.

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Resumen

2017-03-15 03:57:54
2005-004230-40
3160A4-200-WW
A Phase 1/2 Study of SKI-606 in Philadelphia Chromosome Positive LeukemiasEstudio de Fase 1/2 de SKI-606 en Leucemias con Cromosoma Filadelfia Positivo.
3160A4-200-WW

PROMOTORES DEL ENSAYO
Nombre del promotor Organización Persona de contacto País
Wyeth Research Division of Wyeth Pharmaceuticals Inc. United States

Fármacos

  INFORMACIÓN DE FÁRMACOS USADOS:
  FÁRMACO 1:
Test
SKI-606
Capsule*
Oral use

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

Philadelphia Chromosome positive leukemias occur as a result of a reciprocal translocation between chromosomes 9 and 22. Its most common phenotype is Chronic Myelogenous Leukemia, which has three disease phases (chronic, accelerated and blast) of increasi


Part 1 (Dose-escalation part): Define the maximum tolerated dose in subjects with CML in chronic phase resistant to refractory to or intolerant of imatinib, and evaluate the overall PK parameters in this populationPart 2 (Efficacy components): Determine the rate of attaining Major Cytogenetic Response in subjects entering in Chronic Phase, and determine the population PK parameters of this population

Part 1: Determine the rate of Major Cytogenetic Response in Chronic Phase subjects, and obtain data on the ability of SKI-606 to inhibit CrkL and Bcr-Abl at various dose levels of SKI-606.Part 2: Determine the time to progression in subjects beginning in Chronic Phase

Information no disponible en EudraCT


1) Cytologic or PCR based diagnosis of any phase of Ph+ CML or Ph+ ALL who are primarily refractory to full-dose imatinib (600 mg), have disease progression/relapse while on full-dose imatinib, or are intolerant of any dose of imatinib. a. Intolerant is defined as subjects unable to take imatinib due to grade ?3 toxicity or persistent grade 2 toxicity that is not responding to adequate supportive treatment and/or imatinib dose adjustments. b. Relapsed disease will include subjects who have failed to maintain a major cytogenetic response, or failed to maintain any hematologic response. c. Refractory is defined as subjects who fail to achieve adequate response while taking full-dose imatinib. (see #3 for adequate responses) d. In the case that a subject progresses on less than full-dose imatinib, (but at least 300mg daily, or lower if combined with chemotherapy), and cannot receive a higher dose of imatinib due to previous toxicity thought to be due to imatinib, that subject will be eligible for this study.2) Duration of imatinib treatment must conform to the following: a. Subjects started on imatinib in chronic phase who fail to achieve or have failed to maintain a CHR after 12 weeks of full-dose therapy, any cytogenetic response by 26 weeks, or a major cytogenetic response by 12 months. Subjects previously confirmed as responses in any of these categories that have a confirmed loss of their response during the first year are eligible. b. Any subject progressing from Chronic or better to Accelerated or Blast Phase after at least 4 weeks of imatinib treatment immediately qualifies for SKI-606 study inclusion. c. Subjects started on imatinib in accelerated or blastic phase who fail to achieve a return to chronic phase by 12 weeks of imatinib at full dose (?600 mg/day) is eligible. d. Ph positive Acute Lymphocytic Leukemia subjects who fail to attain remission by 8 weeks, or subsequently lose progress from a state of remission.3) ECOG Performance Status of 0 or 1 for Chronic Phase subjects, and 0,1 or 2 for Advanced Stage Subjects4) At least 7 days since prior imatinib treatment5) In part 1, no prior exposure to Src, Abl, or Src/Abl kinase inhibitors is allowed. In Part 2, a maximum of five subjects entering in Chronic Phase, and ten subjects entering in Advanced Phases with a history of any prior exposure to experimental Abl, or Src/Abl inhibitors will be allowed. Discussion of these subjects with the Global Medical Monitor must occur before patient dosing with SKI-606. In these cases at least 10 half lives or 21 days must have passed since previous Src, experimental Abl, or Src/Abl kinase inhibitor treatment, whichever is longer.After these 15 subjects have been enrolled, no prior exposure to Src, Abl or Src/Abl kinase inhibitors is allowed.6) At least 21 days since any other anti-proliferative treatment, (Except Hydroxyurea & Anagrelide – see concomitant medications) including any other investigational agents. For subjects with advanced phase acute leukemia and rapidly progressing disease, this limit could be decreased to 2 weeks, after consulting with the Global Medical Monitor. In these cases, however, toxicities must be grade 1 or better to permit study inclusion and SKI-606 dosing.7) Recovered to Grade 0-1, or to baseline, from any toxicities of prior treatment, other than alopecia8) At least 4 months post stem cell transplantation9) Adequate bone marrow function in Part 1 a. Absolute neutrophil count > 1000/mm3 (Chronic Phase subjects only) b. Platelets > 100,000/mm3 (>100 x109/L) absent any platelet transfusions during the preceding 14 days. (Chronic Phase subjects only)10) Adequate hepatic, and renal function a. AST/ALT < 2.5 x upper limit of normal (ULN) or < 5 x ULN if attributable to liver involvement of leukemia b. Total bilirubin < 1.5 x ULN c. Creatinine < 1.5 x ULN12) Age >18 years13) Documented normal INR, or target INR on three consecutive measurements for subjects maintained on warfarin (Part 2)

1) Subjects with Philadelphia chromosome, and bcr-abl negative CML.2) Subjects previously intolerant of imatinib – Part 1 (dose escalation only)3) Overt leptomeningeal leukemia. Subjects must be free of CNS involvement for a minimum of 6 months. Subjects with CNS symptoms must have a diagnostic lumbar puncture prior to study enrollment.4) Subjects without evidence of leukemia in bone marrow (extramedullary disease only).5) Ongoing requirement for warfarin (Part 1 only)6) Ongoing requirement for hydroxyurea or anagrelide7) Prior exposure to src or abl kinase inhibitors (other than imatinib) except in Part 2 as specified below: Up to five chronic phase and ten advanced phase (AP/BP/ALL) subjects with previous src/abl (other than SKI-606) will be allowed.8) Major surgery or radiotherapy within 14 days before the first dose of SKI-606 (recovery from any previous surgery should be complete before day 1) 9) Ongoing clinical requirement for administration of a strong inhibitor of CYP-3A4 10) A history of ventricular arrhythmia, congenital or acquired prolonged QT interval, a baseline QTc > 0.45 sec or unexplained syncope11) Concomitant use of or need for medications known to prolong the QT interval12) Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval13) Recent (within 30 days of study entry) or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, short bowel syndrome, bleeding, or Grade >1 diarrhea, nausea or emesis)

Response rate as defined by percentage of chronic phase subjects attaining a Major Cytogenetic Response by one year

Fase IFase II
  DISEÑO DEL ENSAYO:

No
No

No
No

No
No

No
No
  COMPARADOR DEL ENSAYO CONTROLADO:

No
No

No
No

Si

Centros participantes:


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

2
3
  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:


30

Para estudios internacionales:


60
120

Investigadores

  INVESTIGADORES QUE PARTICIPAN EN EL ESTUDIO

Estado actual


EC Finalizado



EC Finalizado