A Phase Ib Study of Panobinostat (LBH589) in Combination With 5-Azacitidine for Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML) Patients

Novartis

Status and phase: Completed; Phase 1

Conditions: Acute Myeloid Leukemia (AML); Chronic Myelomonocytic Leukemia (CMML); Myelodysplastic Syndromes (MDS)

Treatments: Drug: Panobinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01613976

CLBH589H1101

Details and patient eligibility

About

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).

Enrollment: 10 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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)

6. 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Panobinostat and Azacitidine

Experimental group

Description:

combination regimen

Treatment:

Drug: Panobinostat