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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Panobinostat and Azacitidine | Experimental | combination regimen |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Panobinostat | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Dose Limiting Toxicitiy(DLT) | DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days) | first 5 weeks of treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| 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 |
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Inclusion Criteria:
Japanese patients who are candidates for treatment with 5-Aza and present with one of the following:
Patient has an ECOG performance status of ≤ 2
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:
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/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Nagoya | Aichi-ken | 460-0001 | Japan | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28905323 | Derived | Kobayashi Y, Munakata W, Ogura M, Uchida T, Taniwaki M, Kobayashi T, Shimada F, Yonemura M, Matsuoka F, Tajima T, Yakushijin K, Minami H. Phase I study of panobinostat and 5-azacitidine in Japanese patients with myelodysplastic syndrome or chronic myelomonocytic leukemia. Int J Hematol. 2018 Jan;107(1):83-91. doi: 10.1007/s12185-017-2327-9. Epub 2017 Sep 13. |
| Label | URL |
|---|---|
| Novartis results database | View source |
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| 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 - 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 |
| 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) | Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03. | Participants will be followed for the duration of treatment, an expected average of 6 months |
| Laboratory abnormalities | duration of treatment, an expected average of 6 months |
| Nagoya |
| Aichi-ken |
| 466-8650 |
| Japan |
| Novartis Investigative Site | Kobe | Hyōgo | 650-0017 | Japan |
| Novartis Investigative Site | Sendai | Miyagi | 980-8574 | Japan |
| Novartis Investigative Site | Chuo-ku | Tokyo | 104-0045 | Japan |
| Novartis Investigative Site | Kyoto | 602-8566 | Japan |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077767 | Panobinostat |
| ID | Term |
|---|---|
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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