Phase 2
Completed N=31
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).
Source: ClinicalTrials.gov NCT00946647 ↗Enrolled (actual)
31
Serious AEs
73.9%
Results posted
Jun 2020
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicity (DLT) (Phase lb) — 1; 3; 2 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicity (DLT) (Phase lb) |
1; 3; 2 | — |
| PRIMARY Number of Dose Limiting Toxicity (DLT) (Phase lb) |
2; 6; 4 | — |
| PRIMARY Composite Complete Response (Phase Llb) |
27.5; 14.3 | — |
| SECONDARY Clinical Response Other Than Composite Clinical Response for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb) |
41.9; 41.4 | — |
| SECONDARY Clinical Response Other Than Composite Clinical Response for Acute Myelogenous Leukemia (AML) Patients Per Investigator (Phase Llb) |
22.2; 30.8 | — |
| SECONDARY Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With MDS/CMML Per Investigator (Phase Llb) |
41.9; 41.4; 16.1; 6.9; 12.9; 3.4 | — |
| SECONDARY Overall Response Rate (ORR) Assessed by Best Overall Response: Participants With AML Per Investigator (Phase Llb) |
22.2; 30.8; 11.1; 15.4; 11.1; 7.7 | — |
| SECONDARY Hematologic Improvement (HI) for Myeloid Dysplastic Syndromes(MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Per Investigator (Phase Llb) |
25.8; 31.0; 35.5; 24.1; 19.4; 13.8 | — |
| SECONDARY 1-year Survival Rate (Phase Llb) |
14.9; 15.6 | — |
| SECONDARY Time to Progression (TTP) (Phase Llb) |
NA; 15.2 | — |
Eligibility Criteria
Inclusion Criteria
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.
Exclusion Criteria
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 ( 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
Data sourced from ClinicalTrials.gov (NCT00946647). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.