Trial of PXD101 (Belinostat) in Combination With Idarubicin to Treat AML Not Suitable for Standard Intensive Therapy
Information source: Onxeo
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Myeloid Leukemia
Intervention: PXD101 (Drug); idarubicin (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: Onxeo Official(s) and/or principal investigator(s): e-mail contact via enquiries@topotarget.com, Study Chair, Affiliation: Onxeo
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.
Clinical Details
Official title: A Phase I/II Clinical Trial of PXD101 in Combination With Idarubicin in Patients With AML Not Suitable for Standard Intensive Therapy
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum Tolerated Dose, Dose Limiting ToxicityOverall Response
Secondary outcome: Time to Response (CR and PR)Duration of Response (CR and PR) Overall Survival Relapse-Free Survival Event-Free Survival Remission Duration Belinostat Cmax Belinostat AUC (Area Under Curve) Elimination t½
Detailed description:
This trial is an open-label, multi-centre, dose-escalation Phase I/II study to evaluate
safety, explore efficacy, pharmacodynamics, and pharmacokinetics of the combination of
PXD101 with idarubicin administered in two different schedules in patients with AML. The
PXD101 plus idarubicin treatment will be repeated at suitable intervals (target is every 3
weeks for schedule A and every 2 weeks for schedule B) depending upon toxicities or disease
progression. Safety and efficacy assessments will be performed at every cycle.
Schedule A uses PXD101 by 30 min infusion daily for 5 days every 3 weeks with escalating
doses of idarubicin.
Schedule B uses escalating doses of continuous infusion (48h) of PXD101 alone or in
combination with idarubicin.
In both regimens the trial may be expanded at the Maximum Tolerated Dose (MTD).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria: (abbreviated)
1. Signed consent
2. AML patients:
1. above 60 years in first relapse or refractory.
2. 18-60 years 2nd relapse or refractory to at least two intensive chemotherapy
regimens.
3. 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.
3. Performance status (ECOG) ≤ 2
4. Age ≥ 18 years
5. Acceptable liver, renal and bone marrow function as defined
6. Serum potassium within normal range.
7. Acceptable coagulation status as defined
8. Precautions for female patients with reproductive potential as defined
Exclusion Criteria:
1. Treatment with investigational agents within the last 4 weeks
2. Prior treatment with HDAC (Histone deacetylases) inhibitors including valproic acid
3. Prior anti-leukemic therapy (except hydroxyurea) within the last 3 weeks of trial
dosing
4. Co-existing active infection (including HIV) or any co-existing medical condition
likely to interfere with trial procedures, including significant cardiovascular
disease
5. Altered mental status precluding understanding of the informed consent process and/or
completion of the necessary study procedures.
6. Concurrent second malignancy.
7. History of hypersensitivity to idarubicin
8. Cumulative idarubicin dose exceeding 100 mg/m², or a (with respect cardiotoxicity)
corresponding dose of other anthracyclines
9. LVEF (left ventricular ejection fraction) below normal range (< 45% )
10. Known Central Nervous System (CNS) leukemia
Locations and Contacts
CHU Lapeyronie, Montpellier 34295, France
Hôpital St. Louis, Paris 75475, France
Uniklinik Homburg, Homburg 66424, Germany
Uni Hospital Marburg, Marburg 35043, Germany
Universitätsklinikum Ulm, Ulm 89081, Germany
Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom
Additional Information
Starting date: August 2007
Last updated: July 6, 2015
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