A phase II, multicentre study of oral LBH589 in patients with accelerated phase or blast phase (blast crisis) chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors
- Conditions
- CMLchronic leukemia10018865
- Registration Number
- NL-OMON30451
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 3
- Patients with diagnosis of Ph+ chronic phase CML (Accelerate phase or blast crisis)
- No evidence of extramedullary leukemic involvement with the exception of liver
or spleen involvement
- Patients 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 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. Patients who are in chronic phase
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;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective is to assess the hematologic response rate and return to<br /><br>chronic phase rate in patients with accelerate phase or blasts crisis when<br /><br>treated with oral LBH589.<br /><br>Efficacy measurements will be the bone marrow assessments for cytogenetic<br /><br>response, peripheral blood sampling for marrow response and complete<br /><br>hematological response and by assessment of extramedullary disease.</p><br>
- Secondary Outcome Measures
Name Time Method <p>CHR rate, overall and complete cytogenetic response rate, major molecular<br /><br>response rate, and complete molecular response rate will be calculated. In<br /><br>addition median progression-free survival time and median duration of major<br /><br>cytogenetic response will be estimated.<br /><br><br /><br>Safety will be evaluated using assessment of adverse events and laboratory<br /><br>data. The assessment of safety will be based mainly on the frequency of adverse<br /><br>events and on the number of laboratory values that are new or worsening based<br /><br>on the CTCAE Grade</p><br>