A Phase Ib/IIb, Open-label, Multi-center, Study of Oral Panobinostat Administered With 5-Azacitidine (in Adult Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML).
2 other identifiers
interventional
113
14 countries
38
Brief Summary
The purpose of this randomized, two-arm, open-label expansion phase study was to collect preliminary efficacy data of panobinostat at the recommended phase II dose (RPIID) level in combination with azacytidine (5-Aza) versus an active control arm 5-Aza alone. This randomized phase II part also allowed collecting safety data of panobinostat in combination with 5-Aza in comparison to single-agent 5-aza.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2009
Longer than P75 for phase_1
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 7, 2009
CompletedFirst Posted
Study publicly available on registry
July 27, 2009
CompletedStudy Start
First participant enrolled
December 2, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 29, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 29, 2019
CompletedResults Posted
Study results publicly available
June 23, 2020
CompletedAugust 4, 2020
July 1, 2020
9.4 years
July 7, 2009
April 29, 2020
July 20, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of Participants With Dose Limiting Toxicity (DLT) (Phase lb)
Dose limiting toxicity (DLT) was defined as a toxicity requiring treatment withdrawal and included the following: Non-hematologic toxicity qualifying for DLT and Hematologic toxicity qualifying for DLT
within the first 28 days (cycle 1)
Number of Dose Limiting Toxicity (DLT) (Phase lb)
Dose limiting toxicity (DLT) was defined as a toxicity requiring treatment withdrawal and included the following: Non-hematologic toxicity qualifying for DLT and Hematologic toxicity qualifying for DLT
within the first 28 days (cycle 1)
Composite Complete Response (Phase Llb)
Composite complete response is defined as complete response (CR), Complete response with incomplete blood count recovery (CRi) or bone marrow complete response (BM-CR) as defined by the International Working Group (IWG) response criteria.
48 months
Secondary Outcomes (7)
Clinical Response Other Than Composite Clinical Response for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb)
48 months
Clinical Response Other Than Composite Clinical Response for Acute Myelogenous Leukemia (AML) Patients Per Investigator (Phase Llb)
48 months
Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With MDS/CMML Per Investigator (Phase Llb)
48 months
Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With AML Per Investigator (Phase Llb)
48 months
Hematologic Improvement (HI) for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb)
48 months
- +2 more secondary outcomes
Study Arms (2)
Panobinostat + 5-Azacytidine
EXPERIMENTALIn phase I: Panobinostat : Escalating doses starting with 20 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15. In phase II: Panobinostat : Rapid Phase II doses at 30 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15. In both phases, dose of 5-Azacytidine was 75 mg/m\^2, subcutaneously Daily for Day 1 to Day 7.
5-Azacytidine
ACTIVE COMPARATORThe dose of 5-Aza was fixed at 75 mg/m2/day for 7 days in Week 1 of each cycle. 5-Aza was sourced locally, except in 4 countries (Hungary, Switzerland, UK, and Spain, for which a central purchase was used by Novartis. Dose of 5-Azacytidine : 75 mg/m\^2 subcutaneously daily from Day 1 to Day 7.
Interventions
Panobinostat was supplied by Novartis as immediate-release hard gelatin capsules in strengths of 5 mg, 10 mg, and 20 mg packaged in high density polyethylene bottles.
Eligibility Criteria
You may qualify if:
- Phase l:
- Patients with cytopathologically confirmed diagnosis of AML according to WHO criteria, excluding acute promyelocytic leukemia who are eligible for Vidaza treatment
- ECOG performance status greater less than or equal to 2
- Phase ll:
- Adult patients (age ≥ 18 years) who were candidates for treatment with 5-Aza and present with one of the following:
- intermediate-2 or high-risk myelodysplastic syndromes 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
- chronic myelomonocytic leukemia (CMML)
- Patients must have had 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 within normal ranges (WNL) for the institution.
You may not qualify if:
- Phase l:
- Prior treatment with deacetylase inhibitors
- Concurrent therapy with any other investigational agent
- Phase ll:
- Planned hematopoietic stem-cell transplantation (HSCT)
- Patients with therapy-related MDS
- Patients with therapy-related AML and/or relapsed/refractory AML
- Patients with impaired cardiac function including any of the following:
- Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmia, clinically significant resting bradycardia (\<50 beats per minute), QTcF \> 460 ms on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
- Previous history of angina pectoris or acute MI within 6 months
- Screening LVEF \<45% by echocardiography or MUGA
- Other clinically significant heart disease (e.g. uncontrolled hypertension or history of poor compliance with an antihypertensive regimen).
- Any of concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study. For example:
- Uncontrolled diabetes
- Active or uncontrolled infection
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (38)
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, 30912, United States
Goshen Center for Cancer Care IU Cancer Center
Indianapolis, Indiana, 46202, United States
University of Kansas Hospital and Medical Center SC - Univ KS
Kansas City, Kansas, 66160, United States
Dana Farber Cancer Institute Beth Israel Deaconess Med Ctr
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Sloan Kettering 2
New York, New York, 10017, United States
Cleveland Clinic Foundation Cleve Clinic
Cleveland, Ohio, 44195, United States
Medical University of South Carolina -Hollings Cancer Center MUSC
Charleston, South Carolina, 29425, United States
University of Texas MD Anderson Cancer Center Dept of MD Anderson (16)
Houston, Texas, 77030, United States
Novartis Investigative Site
Innsbruck, A-6020, Austria
Novartis Investigative Site
Vienna, A-1100, Austria
Novartis Investigative Site
Bruges, 8000, Belgium
Novartis Investigative Site
Yvoir, 5530, Belgium
Novartis Investigative Site
Edmonton, Alberta, T6G 2B7, Canada
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site
Bobigny, 93009, France
Novartis Investigative Site
Frankfurt, 60590, Germany
Novartis Investigative Site
Freiburg im Breisgau, 79106, Germany
Novartis Investigative Site
Budapest, 1097, Hungary
Novartis Investigative Site
Debrecen, 4032, Hungary
Novartis Investigative Site
Kaposvár, 7400, Hungary
Novartis Investigative Site
Szeged, H 6725, Hungary
Novartis Investigative Site
Florence, FI, 50134, Italy
Novartis Investigative Site
Reggio Calabria, RC, 89124, Italy
Novartis Investigative Site
Roma, RM, 00161, Italy
Novartis Investigative Site
Seoul, Korea, 05505, South Korea
Novartis Investigative Site
Seoul, 06351, South Korea
Novartis Investigative Site
Málaga, Andalusia, 29010, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Madrid, 28006, Spain
Novartis Investigative Site
Gothenburg, 413 45, Sweden
Novartis Investigative Site
Stockholm, SE-118 83, Sweden
Novartis Investigative Site
Basel, 4031, Switzerland
Novartis Investigative Site
Geneva, 1205, Switzerland
Novartis Investigative Site
Sankt Gallen, 9007, Switzerland
Novartis Investigative Site
Bangkok, 10330, Thailand
Novartis Investigative Site
Bangkok, 10700, Thailand
Novartis Investigative Site
London, EC1A 7BE, United Kingdom
Novartis Investigative Site
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (1)
Garcia-Manero G, Sekeres MA, Egyed M, Breccia M, Graux C, Cavenagh JD, Salman H, Illes A, Fenaux P, DeAngelo DJ, Stauder R, Yee K, Zhu N, Lee JH, Valcarcel D, MacWhannell A, Borbenyi Z, Gazi L, Acharyya S, Ide S, Marker M, Ottmann OG. A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts. Leukemia. 2017 Dec;31(12):2799-2806. doi: 10.1038/leu.2017.159. Epub 2017 May 26.
PMID: 28546581DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Treatment was assigned sequentially for the initial dose escalation part (phase Ib): If a dose was safe, the next cohort started with the next dose level. Randomization applies only for the phase IIb part.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 7, 2009
First Posted
July 27, 2009
Study Start
December 2, 2009
Primary Completion
April 29, 2019
Study Completion
April 29, 2019
Last Updated
August 4, 2020
Results First Posted
June 23, 2020
Record last verified: 2020-07
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.