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

Acute Myeloid Leukemia (AML) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01613976
• Other study ID #: CLBH589H1101
• Status: Completed
• Phase: Phase 1
• Start date: August 2012
• Est. completion date: May 2014

Study information

• Verified date: December 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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/exclusion criteria may apply

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Chronic Myelomonocytic Leukemia (CMML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes (MDS)
• Preleukemia
• Syndrome

Intervention

Drug:
• Panobinostat

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Sendai-city	Miyagi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Trough level of PAN in combination with 5-Aza		Day 4, 5, 8 of the 1st cycle; pre-dose (0 hour)
Secondary	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
Secondary	Laboratory abnormalities		duration of treatment, an expected average of 6 months

External Links

•   Novartis results database