Back to resultsA 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
Primary Purpose
Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Panobinostat
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes (MDS) focused on measuring Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Panobinostat, LBH589, 5-Aza, Azacitidine
Eligibility Criteria
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)
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panobinostat and Azacitidine
Arm Description
combination regimen
Outcomes
Primary Outcome Measures
Incidence of Dose Limiting Toxicitiy(DLT)
DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)
Secondary Outcome Measures
PK parameter - Cmax
PK parameter - Tmax
PK parameter - AUC (AUC0-48, AUC0-tlast)
PK parameter - T1/2 (apparent oral clearance, volume distribution)
PK parameter - AUC0-inf
Trough level of PAN in combination with 5-Aza
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.
Laboratory abnormalities
Full Information
NCT ID
NCT01613976
First Posted
May 24, 2012
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01613976
Brief Title
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
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 Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
Keywords
Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Panobinostat, LBH589, 5-Aza, Azacitidine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panobinostat and Azacitidine
Arm Type
Experimental
Arm Description
combination regimen
Intervention Type
Drug
Intervention Name(s)
Panobinostat
Other Intervention Name(s)
LBH589
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicitiy(DLT)
Description
DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)
Time Frame
first 5 weeks of treatment period
Secondary Outcome Measure Information:
Title
PK parameter - Cmax
Time Frame
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
Title
PK parameter - Tmax
Time Frame
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
Title
PK parameter - AUC (AUC0-48, AUC0-tlast)
Time Frame
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
Title
PK parameter - T1/2 (apparent oral clearance, volume distribution)
Time Frame
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
Title
PK parameter - AUC0-inf
Time Frame
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
Title
Trough level of PAN in combination with 5-Aza
Time Frame
Day 4, 5, 8 of the 1st cycle; pre-dose (0 hour)
Title
Frequency and severity of Adverse Events (AEs)
Description
Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03.
Time Frame
Participants will be followed for the duration of treatment, an expected average of 6 months
Title
Laboratory abnormalities
Time Frame
duration of treatment, an expected average of 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Nagoya-city
State/Province
Aichi
ZIP/Postal Code
466-8650
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
460-0001
Country
Japan
Facility Name
Novartis Investigative Site
City
Kobe-city
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai-city
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Novartis Investigative Site
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
28905323
Citation
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.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13549
Description
Novartis results database
Learn more about this trial
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
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