A phase II, multicentre study of oral LBH589 in patients with chronic phase chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors - Oral LBH589 for treatment of TKI inhibitor resistant chronic phase CM

ovartis0 个研究点目标入组 5 人开始时间: 待定最近更新: 2024年6月18日

适应症

试验速览

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•- Patients with diagnosis of Ph+ chronic phase CML (CP-CML)
•- No evidence of extramedullary leukemic involvement with the exception of liver
•or spleen involvement
•- Patients with CP-CML must have received treatment with at least two BCR-ABL kinase inhibitors and have demonstrated resistance to the most recent BCR-ABL kinase inhibitor
•*Patients with a history of intolerance to one or two BCR-ABL kinase inhibitors
•are eligible if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor
•* Patients who are intolerant of at least 2 BCR-ABL kinase inhibitors must also demonstrate resistance to or intolerance of interferon-alpha (IFN-*) / cytarabine
•- Patients must meet the following laboratory criteria:
•* Serum albumin > 3g/dL
•* AST/SGOT and ALT/SGPT * 2.5 x upper limit of normal (ULN) ) or * 5.0 x ULN if
•the transaminase elevation is due to leukemic involvement
•* Serum bilirubin * 1.5 x ULN
•* Serum creatinine * 1.5 x ULN or 24-hour creatinine clearance * 50 ml/min
•* Serum potassium, phosphorus, total calcium, magnesium * LLN
•* TSH and free T4 within normal limits (thyroid hormone replacement is allowed)
•- Baseline MUGA or ECHO must demonstrate LVEF * lower limit normal.
•- ECOG Performance Status of * 2

•1. A candidate for stem cell transplantation (with appropriate donor)
•2. Prior treatment with an HDAC inhibitor
•3. A prior history of accelerated phase or blast crisis CML
•4. Impaired cardiac function including :Screening ECG with a QTc > 450 msec, congenital long QT syndrome, history of sustained ventricular tachycardia, history of ventricular fibrillation or torsades de pointes, bradycardia (< 50 beats per minute), myocardial infarction or unstable angina within 6 months of studyentry, congestive heart failure (NYHA class III or IV), right bundle branch block and left anterior hemiblock, uncontrolled hypertension
•5. Concomitant use of drugs with a risk of causing torsades de pointes
•6. Concomitant use of CYP3A4 inhibitors
•7. Patients with unresolved diarrhea > CTCAE grade 1
•8. Impairment of gastrointestinal (GI) function that may significantly alter the absorption of oral LBH589
•9. Other concurrent severe and/or uncontrolled medical conditions
•10. Chemotherapy, any investigational drug or major surgery < 4 weeks prior to starstudy drug
•11. BCR-ABL kinase inhibitor * 1 week of first treatment with LBH589
•12. Concomitant use of any anti-cancer therapy or radiation therapy. Hydroxyurea, Agrylin (anagrelide) or leukaphereses is permitted at the investigators discretion
•13. Active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin or any other anti-vitamin K drug.
•14. HIV positiv or hepatitis C;

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