Myelodysplastic SyndromesPhase 1/2NCT00946647
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).
A Phase 1/2 study testing Panobinostat (LBH589) and 5-Azacytidine in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Novartis Pharmaceuticals at 38 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia
- What is being tested?
- Panobinostat (LBH589) and 5-Azacytidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 38 sitesin 14 countries
- Study dates
- 2 Dec 2009to 29 Apr 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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)
- Presence of unstable atrial fibrillation (ventricular response rate >100 bpm). Patients with stable atrial fibrillation are eligible provided they do not meet the other cardiac exclusion criteria
- 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
- Uncontrolled hypothyroidism
- Acute or chronic liver or renal disease
- Patient had evidence of clinically significant mucosal or internal bleeding
Trial locations and contacts
38 sites in 14 countries.
38 sites in 14 countries
United States8 sites
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, 30912
Dana Farber Cancer Institute Beth Israel Deaconess Med Ctr
Boston, Massachusetts, 02215
Medical University of South Carolina -Hollings Cancer Center MUSC
Charleston, South Carolina, 29425
Cleveland Clinic Foundation Cleve Clinic
Cleveland, Ohio, 44195
University of Texas MD Anderson Cancer Center Dept of MD Anderson (16)
Houston, Texas, 77030
Goshen Center for Cancer Care IU Cancer Center
Indianapolis, Indiana, 46202
University of Kansas Hospital and Medical Center SC - Univ KS
Kansas City, Kansas, 66160
Memorial Sloan Kettering Sloan Kettering 2
New York, New York, 10017
Hungary4 sites
Novartis Investigative Site
Budapest, 1097
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Kaposvár, 7400
Novartis Investigative Site
Szeged, H 6725
Italy3 sites
Novartis Investigative Site
Florence, FI, 50134
Novartis Investigative Site
Reggio Calabria, RC, 89124
Novartis Investigative Site
Roma, RM, 00161
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28006
Novartis Investigative Site
Málaga, Andalusia, 29010
Switzerland3 sites
Novartis Investigative Site
Basel, 4031
Novartis Investigative Site
Geneva, 1205
Novartis Investigative Site
Sankt Gallen, 9007
Austria2 sites
Novartis Investigative Site
Innsbruck, A-6020
Novartis Investigative Site
Vienna, A-1100
Belgium2 sites
Novartis Investigative Site
Bruges, 8000
Novartis Investigative Site
Yvoir, 5530
Canada2 sites
Novartis Investigative Site
Edmonton, Alberta, T6G 2B7
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Germany2 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Freiburg im Breisgau, 79106
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, 06351
Sweden2 sites
Novartis Investigative Site
Gothenburg, 413 45
Novartis Investigative Site
Stockholm, SE-118 83
Thailand2 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10700
United Kingdom2 sites
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
Wolverhampton, WV10 0QP
About this study
Official title: A Phase Ib/IIb, Open-label, Multi-center, Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (in Adult Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML).
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.
Read the detailed description
The primary objective of the phase lb portion of this study was to determine the maximum tolerated dose (MTD )and/or recommended phase ll dose (RPIID) of oral panobinostat in combination with a fixed dose of 5-Aza in adult patients with International Prognostic Scoring System intermediate-2 (IPSS INT-2) or high risk myelodysplastic syndrome (MDS), Chronic myelomonocytic leukemia (CMML), or Acute myelogenous leukemia (AML).
The primary objective of the phase llb portion of this study was to assess preliminary efficacy of treatment with the panobinostat and 5-Aza combination at the RPIID relative to treatment with single agent 5-Aza through the assessment of composite CR (complete response (CR) or CRi or bone marrow CR).
In the phase lb phase of the study, the patients received escalating oral doses of panobinostat commencing in Cycle 1. The starting dose for panobinostat was 20 mg/day administered orally commencing on Day 3. Each treatment cycle consisted of 28 days (4 weeks). In each cycle, panobinostat was administered twice in Week 1 (Day 3, Day 5), thrice in Week 2 (Day 8, Day 10, and Day 12) and once in Week 3 (Day 15), with no dosing in Week 4. Successive cohorts of patients received escalating doses of panobinostat until the MTD/RPIID was determined. The dose of 5-Aza was fixed at 75 mg/m2/day for 7 days in Week 1 of each cycle.
After the MTD/RPIID was determined, enrollment in the Phase Ib part was closed and the Phase IIb part of the study commenced. Ongoing patients from the Phase Ib part continued their treatment at the assigned dose level according to the regimen and schedule for the Phase Ib part.
Once the RPIID was defined in Phase Ib, additional 80 patients were to be enrolled into the Phase IIb part of the study and randomly assigned in a 1:1 ratio receiving the RPIID of panobinostat plus 5-Aza (investigational arm) or single agent 5-Aza (active control arm). The treatment schedule for the investigational arm was the same as that for the Phase Ib. Single agent 5-Aza (active control arm) was administered according to the locally approved label (75mg/m2 daily for 7 days). Patients continued treatment until disease progression, unacceptable toxicity or consent withdrawal, whichever came first.
- Being tested
- Panobinostat (LBH589), 5-Azacytidine
- Keywords
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia, hypomethylating therapy, deacetylase inhibitor, MDS, CMML, AML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Panobinostat (LBH589)Drug
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.
5-AzacytidineDrug
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat + 5-Azacytidine | Experimental | In 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. Receives: Drug: Panobinostat (LBH589); Drug: 5-Azacytidine |
| 5-Azacytidine | Active comparator | The 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. Receives: Drug: 5-Azacytidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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)
This is the best overall response as measured by Clinical response. Clinical response is defined as having complete remission (CR), bone marrow complete remission (BM-CR), partial remission or hematologic improvement (HI) as defined by the International Working Group (IWG) response criteria.
Measured: 48 months
Clinical Response Other Than Composite Clinical Response for Acute Myelogenous Leukemia (AML) Patients Per Investigator (Phase Llb)
This is the best overall response as measured by Clinical response. Clinical response is defined as having complete remission (CR), complete remission with incomplete blood count recovery (CRi) or partial remission as defined by the International Working Group (IWG) response criteria.
Measured: 48 months
Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With MDS/CMML Per Investigator (Phase Llb)
Best overall response as measured by complete remission (CR) or bone marrow CR (BM-CR) or partial remission (PR) or hematologic improvement (HI).
Overall response patients achieved other than the composite CR by individual response category: CR, CRi, mCR or PR as defined by the International Working Group (IWG) response criteria.
Measured: 48 months
Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With AML Per Investigator (Phase Llb)
Best overall response as measured by complete remission (CR) or complete response with incomplete blood count recovery (CRi) or partial remission (PR).
Overall response patients achieved other than the composite CR by individual response category: CR, CRi or PR.
Measured: 48 months
Hematologic Improvement (HI) for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb)
Hematologic response consists of Erythroid response (HI-E), Platelet response (HI-P) and Neutrophil response (HI-N).
HI-E: Hgb increase by ≥ 1.5 g/dL over pretreatment \& relevant reduction of units of RBC transfusions by an absolute number of at least 4 units of PRBCs/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation.
HI-P: Absolute increase of ≥ 30 x 109/L over pretreatment or patients starting with ≥ 20 x 109/L platelets OR increase from <20 x 109/L at pretreatment to > 20 x 109/L and by at least 100%.
HI-N: At least 100% increase and an absolute increase > 0.5 x 109/L over pretreatment value.
Measured: 48 months
1-year Survival Rate (Phase Llb)
Overall survival was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact. Patients not known to have died were censored for 'Lost to follow-up' if the time between their last contact date and the analysis cut-off date was longer than 3 months and 2 weeks (104 days) during the first year after study evaluation completion, and longer than 6 months and 2 weeks (194 days), thereafter. The 1-year survival rate was obtained from the Kaplan-Meier analysis of overall survival, and its variance was estimated by Greenwood's formula.
Measured: 12 months
Time to Progression (TTP) (Phase Llb)
Time to progression (TTP) was defined as the time from the date of randomization to the date of the first documented PD per investigator's assessment or death due to study indication.
Time to progression was analyzed by the Kaplan Meier method. Based on the Guidelines for Implementation of international working group (IWG) response criteria in AML, MDS and CMML according to Cheson 2003 and 2006.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2009 (estimated)
- Study start2 Dec 2009
- Primary completion29 Apr 2019
- Study completion29 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00946647
- Sponsor's protocol ID
- CLBH589H2101
- Other IDs
- 2009-010548-32, 2009
- Status last verified
- Jul 2020
- First submitted
- 7 Jul 2009
- Last updated
- 4 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 28546581
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/IIb, Open-label, Multi-center, Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (in Adult Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML).
- ClinicalTrials.gov ID
- NCT00946647
- Acronym / sponsor ID
- CLBH589H2101
- Keywords
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia, hypomethylating therapy, deacetylase inhibitor, MDS, CMML, AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Dec 2009 (actual)
- Primary completion
- 29 Apr 2019 (actual)
- Study completion
- 29 Apr 2019 (actual)
- First posted
- 27 Jul 2009 (estimated)
- Results
- Posted 23 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objective of the phase lb portion of this study was to determine the maximum tolerated dose (MTD )and/or recommended phase ll dose (RPIID) of oral panobinostat in combination with a fixed dose of 5-Aza in adult patients with International Prognostic Scoring System intermediate-2 (IPSS INT-2) or high risk myelodysplastic syndrome (MDS), Chronic myelomonocytic leukemia (CMML), or Acute myelogenous leukemia (AML).
The primary objective of the phase llb portion of this study was to assess preliminary efficacy of treatment with the panobinostat and 5-Aza combination at the RPIID relative to treatment with single agent 5-Aza through the assessment of composite CR (complete response (CR) or CRi or bone marrow CR).
In the phase lb phase of the study, the patients received escalating oral doses of panobinostat commencing in Cycle 1. The starting dose for panobinostat was 20 mg/day administered orally commencing on Day 3. Each treatment cycle consisted of 28 days (4 weeks). In each cycle, panobinostat was administered twice in Week 1 (Day 3, Day 5), thrice in Week 2 (Day 8, Day 10, and Day 12) and once in Week 3 (Day 15), with no dosing in Week 4. Successive cohorts of patients received escalating doses of panobinostat until the MTD/RPIID was determined. The dose of 5-Aza was fixed at 75 mg/m2/day for 7 days in Week 1 of each cycle.
After the MTD/RPIID was determined, enrollment in the Phase Ib part was closed and the Phase IIb part of the study commenced. Ongoing patients from the Phase Ib part continued their treatment at the assigned dose level according to the regimen and schedule for the Phase Ib part.
Once the RPIID was defined in Phase Ib, additional 80 patients were to be enrolled into the Phase IIb part of the study and randomly assigned in a 1:1 ratio receiving the RPIID of panobinostat plus 5-Aza (investigational arm) or single agent 5-Aza (active control arm). The treatment schedule for the investigational arm was the same as that for the Phase Ib. Single agent 5-Aza (active control arm) was administered according to the locally approved label (75mg/m2 daily for 7 days). Patients continued treatment until disease progression, unacceptable toxicity or consent withdrawal, whichever came first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Panobinostat + 5-Azacytidine | Experimental | Drug: Panobinostat (LBH589), Drug: 5-AzacytidineIn 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 comparator | Drug: 5-AzacytidineThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
- Adult patients (age ≥ 18 years) who were candidates for treatment with 5-Aza and present with one of the following:
- 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.
Key exclusion criteria (19 listed)
- Prior treatment with deacetylase inhibitors
- Concurrent therapy with any other investigational agent
- Planned hematopoietic stem-cell transplantation (HSCT)
- Patients with therapy-related MDS
- Patients with therapy-related AML and/or relapsed/refractory AML
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Panobinostat (LBH589)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. | Drug | Panobinostat + 5-Azacytidine |
| 5-Azacytidine | Drug | 5-Azacytidine, Panobinostat + 5-Azacytidine |
Primary outcome
Number of Participants With Dose Limiting Toxicity (DLT) (Phase lb)
Time frame: within the first 28 days (cycle 1)
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
Number of Dose Limiting Toxicity (DLT) (Phase lb)
Time frame: within the first 28 days (cycle 1)
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
Composite Complete Response (Phase Llb)
Time frame: 48 months
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.
7 secondary outcomes
Clinical Response Other Than Composite Clinical Response for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb)
Time frame: 48 months
Clinical Response Other Than Composite Clinical Response for Acute Myelogenous Leukemia (AML) Patients Per Investigator (Phase Llb)
Time frame: 48 months
Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With MDS/CMML Per Investigator (Phase Llb)
Time frame: 48 months
Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With AML Per Investigator (Phase Llb)
Time frame: 48 months
Hematologic Improvement (HI) for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb)
Time frame: 48 months
1-year Survival Rate (Phase Llb)
Time frame: 12 months
Time to Progression (TTP) (Phase Llb)
Time frame: 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28546581Garcia-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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
38 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panobinostat (LBH589) and 5-Azacytidine in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Novartis Pharmaceuticals at 38 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Hungary, Italy, Spain, Switzerland and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicity (DLT) (Phase lb) (time frame: within the first 28 days (cycle 1)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00946647, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2020; AzTrials last refreshed its copy on 27 Oct 2026.