Trial of PXD101 in Combination With Idarubicin to Treat Acute Myeloid Leukemia (AML) Not Suitable for Standard Intensive Therapy

This study has been completed.
Information provided by (Responsible Party):
TopoTarget A/S Identifier:
First received: April 7, 2009
Last updated: November 29, 2013
Last verified: November 2013

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.

Condition Intervention Phase
Acute Myeloid Leukemia
Drug: PXD101
Drug: idarubicin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Trial of PXD101 in Combination With Idarubicin in Patients With AML Not Suitable for Standard Intensive Therapy

Resource links provided by NLM:

Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • safety and tolerance (Maximum Tolerated Dose, Dose Limiting Toxicity) and efficacy (Response rate (CR or PR)) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to response, response duration, overall survival, relapse-free survival, event-free survival and remission duration, Pharmacokinetics (PK) and Pharmacodynamics (PHDY) following PXD101 combination therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 41
Study Start Date: August 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A

PXD101 administered as a 30-minute intravenous (IV) infusion of 1000 mg/m²/d for five consecutive days every 3 weeks.

Idarubicin administered on day 5 (first steps) or days 4 and 5 (later steps). Patients will be treated in a 21-day cycle for a minimum of 2 cycles and a maximum of 6 cycles (depending on cumulated idarubicin dose).

Drug: PXD101
Other Name: Belinostat
Drug: idarubicin
Other Name: Zavedos
Experimental: Arm B
PXD101 administered by continuous intravenous infusion over 24-48 hours and idarubicin (in the later steps) added after the first 24 hours. The second cycle will start on day 15 but under observation of possible toxicity. Further cycles will be administered q 14 d for up to 6 cycles. The first dose steps will be carried out with PXD101 alone for safety reasons.
Drug: PXD101
Other Name: Belinostat
Drug: idarubicin
Other Name: Zavedos

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).


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 cycles.
    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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00878722

CHU Lapeyronie
Montpellier, France, 34295
Hôpital St. Louis
Paris, France, 75475
Uniklinik Homburg
Homburg, Germany, 66424
Uni Hospital Marburg
Marburg, Germany, 35043
Universitätsklinikum Ulm
Ulm, Germany, 89081
United Kingdom
Christie Hospital NHS Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
TopoTarget A/S
Principal Investigator: Hervé Dombret, MD Hôpital St. Louis, Paris, France
Principal Investigator: Jean-Francois Rossi, MD CHU Lapeyronie, Montpellier, France
Principal Investigator: Andreas Neubauer, MD Uni Hospital Marburg, Germany
Principal Investigator: Michael Pfreundschuh, MD Uniklinik Homburg, Germany
Principal Investigator: Helmuth Salih, MD University Clinic Tübingen, Germany
Principal Investigator: Mike Dennis, MD Christie Hospital NHS Trust, Manchester, UK
Principal Investigator: Gareth Morgan, MD The Royal Marsden NHS Trust, Surrey, UK
Principal Investigator: Richard Schlenk, MD Universitätsklinikum Ulm, Germany
  More Information

No publications provided

Responsible Party: TopoTarget A/S Identifier: NCT00878722     History of Changes
Other Study ID Numbers: PXD101-CLN-15
Study First Received: April 7, 2009
Last Updated: November 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by TopoTarget A/S:
Acute Myeloid Leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors processed this record on October 29, 2014