Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML), Myelodysplastic Syndromes (MDS)
Conditions
Keywords
Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Panobinostat, LBH589, 5-Aza, Azacitidine
Brief summary
The purpose of this study is to confirm the safety and tolerability of oral panobinostat (PAN) in combination with a fixed dose of 5-Azacitidine (5-Aza) in adult Japanese patients with Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML).
Interventions
DRUGPanobinostat
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Japanese patients who are candidates for treatment with 5-Aza and present with one of the following: * intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). OR * AML with multilineage dysplasia and maximum of 30% blasts (former RAEB-T according to FAB) OR CMML 2. Patient has an ECOG performance status of ≤ 2 3. Patients must have the following laboratory values unless elevations are considered due to MDS or leukemia: AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN; serum creatinine ≤ 1.5 x ULN; serum bilirubin (total and direct) ≤ 2 x ULN; electrolyte panel without clinically relevant abnormalities
Exclusion criteria
1. Patient who is planned for or has history of hematopoietic stem-cell transplantation (HSCT) 2. Patients with relapsed/refractory AML 3. Patient is receiving concurrent anti-cancer therapy 4. Patient has received prior treatment with deacetylase inhibitors (DACi) 5. Patient has received prior treatment with 5-Aza or 6-aza-2'-deoxycytidine (decitabine) 7\. Patient has shown suspected hypersensitivity to 5-Aza or Mannitol 8. Patients with impaired cardiac function 9. Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pontes if such treatment cannot be discontinued or switched to a different medication prior to starting study treatment 10. Patients with clinical evidence of relevant mucosal or internal bleeding 11. Patient has any other concurrent severe and/or uncontrolled medical conditions Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicitiy(DLT) | first 5 weeks of treatment period | DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter - Tmax | Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours | — |
| PK parameter - AUC (AUC0-48, AUC0-tlast) | Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours | — |
| PK parameter - T1/2 (apparent oral clearance, volume distribution) | Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours | — |
| PK parameter - Cmax | Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours | — |
| Trough level of PAN in combination with 5-Aza | Day 4, 5, 8 of the 1st cycle; pre-dose (0 hour) | — |
| Frequency and severity of Adverse Events (AEs) | Participants will be followed for the duration of treatment, an expected average of 6 months | Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03. |
| Laboratory abnormalities | duration of treatment, an expected average of 6 months | — |
| PK parameter - AUC0-inf | Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours | — |
Countries
Japan
Outcome results
None listed