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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01613976

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes (MDS) Chronic Myelomonocytic Leukemia (CMML) Acute Myeloid Leukemia (AML)	Drug: Panobinostat	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (Vidaza®) in Adult Japanese Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML)

Study Start Date :

Aug 1, 2012

Actual Primary Completion Date :

May 1, 2014

Actual Study Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panobinostat and Azacitidine combination regimen	Drug: Panobinostat Other Names: LBH589

Arm

Intervention/Treatment

Experimental: Panobinostat and Azacitidine

combination regimen

Drug: Panobinostat

Other Names:

LBH589

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
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) [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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:

Patient who is planned for or has history of hematopoietic stem-cell transplantation (HSCT)
Patients with relapsed/refractory AML
Patient is receiving concurrent anti-cancer therapy
Patient has received prior treatment with deacetylase inhibitors (DACi)
Patient has received prior treatment with 5-Aza or 6-aza-2'-deoxycytidine (decitabine)
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nagoya-city	Aichi	Japan	466-8650
2	Novartis Investigative Site	Nagoya	Aichi	Japan	460-0001
3	Novartis Investigative Site	Kobe-city	Hyogo	Japan	650-0017
4	Novartis Investigative Site	Sendai-city	Miyagi	Japan	980-8574
5	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	104-0045
6	Novartis Investigative Site	Kyoto		Japan	602-8566