Phase 2
Completed N=41
Trial of PXD101 (Belinostat) in Combination With Idarubicin to Treat AML Not Suitable for Standard Intensive Therapy
Source: ClinicalTrials.gov NCT00878722 ↗Enrolled (actual)
41
Serious AEs
70.7%
Results posted
Nov 2014
Primary outcomePrimary: Maximum Tolerated Dose, Dose Limiting Toxicity — 0; 0; 0; 0 participants
Summary
An open-label, non-randomized, multi-centre, Phase I/II trial to assess the efficacy and safety of 2 schedules of PXD101 in combination with idarubicin in patients with AML not suitable for standard intensive therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose, Dose Limiting Toxicity |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Overall Response |
0; 1; 1; 1; 1; 1 | — |
| SECONDARY Time to Response (CR and PR) |
2.6; 7.9; 6.0; 4.0; 1.9; 4.0 | — |
| SECONDARY Duration of Response (CR and PR) |
26.3; 20.6; 28.1; 5.4; 30.3; 19.6 | — |
| SECONDARY Overall Survival |
10; 4.9; 3.7; 3.9 | — |
| SECONDARY Relapse-Free Survival |
26.3; 20.6; 28.1; 30.3; 6.1 | — |
| SECONDARY Event-Free Survival |
5.1; 3.1; 8.0; 6.5; 2.0; 5.4 | — |
| SECONDARY Remission Duration |
26.3; 20.6; 5.4; 30.3; 19.6; 3.0 | — |
| SECONDARY Belinostat Cmax |
38744; 31952; 9657 | — |
| SECONDARY Belinostat AUC (Area Under Curve) |
21850; 21322; 172823 | — |
| SECONDARY Elimination t½ |
12.7; 13.1; 4.21 | — |
Eligibility Criteria
Inclusion Criteria: (abbreviated)
- Signed consent
- AML patients:
- above 60 years in first relapse or refractory.
- 18-60 years 2nd relapse or refractory to at least two intensive chemotherapy regimens.
- above 60 years with high risk features (cytogenetics, secondary or treatment related AML) d) above 60 years with myelodysplastic syndrome with >10% blasts in bone marrow (WHO RAEB-2 (Refractory anemia with excess blasts-2)). For patients below 60 years potential curative treatments should have been exhausted.
- Performance status (ECOG) ≤ 2
- Age ≥ 18 years
- Acceptable liver, renal and bone marrow function as defined
- Serum potassium within normal range.
- Acceptable coagulation status as defined
- Precautions for female patients with reproductive potential as defined
Exclusion Criteria
- Treatment with investigational agents within the last 4 weeks
- Prior treatment with HDAC (Histone deacetylases) inhibitors including valproic acid
- Prior anti-leukemic therapy (except hydroxyurea) within the last 3 weeks of trial dosing
- Co-existing active infection (including HIV) or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease
- Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.
- Concurrent second malignancy.
- History of hypersensitivity to idarubicin
- Cumulative idarubicin dose exceeding 100 mg/m², or a (with respect cardiotoxicity) corresponding dose of other anthracyclines
- LVEF (left ventricular ejection fraction) below normal range (< 45% )
- Known Central Nervous System (CNS) leukemia
Data sourced from ClinicalTrials.gov (NCT00878722). 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.