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

NCT00878722 | Completed Phase 1 Results

• 1 other identifier: PXD101-CLN-15
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 6

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; PXD101; Belinostat; Idarubicin

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose, Dose Limiting Toxicity

  DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle

  First Cycle

• Overall Response

  Efficacy measured as Response rate (complete response (\[CR\] and Complete remission with incomplete recovery of platelets \[CRi\]) and partial response (\[PR\])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission).

  Throughout study, after each cycle for the first two cycles, then after every second cycle

Secondary Outcomes (9)

• Time to Response (CR and PR)

  Throughout study, after each cycle for the first two cycles, then after every second cycle

• Duration of Response (CR and PR)

  Throughout study, after each cycle for the first two cycles, then after every second cycle

• Overall Survival

  Throughout study, after each cycle for the first two cycles, then after every second cycle

• Relapse-Free Survival

  Throughout study, after each cycle for the first two cycles, then after every second cycle

• Event-Free Survival

  Throughout study, after each cycle for the first two cycles, then after every second cycle

Study Arms (2)

Arm A

EXPERIMENTAL

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; Drug: idarubicin

Arm B

EXPERIMENTAL

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; Drug: idarubicin

Interventions

PXD101 DRUG

Also known as: Belinostat

Arm A; Arm B

idarubicin DRUG

Also known as: Zavedos

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed consent
• AML patients:
• above 60 years in first relapse or refractory.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Valerio Therapeutics: lead

Study Sites (6)

CHU Lapeyronie

Montpellier, 34295, France

Location

Hôpital St. Louis

Paris, 75475, France

Location

Uniklinik Homburg

Homburg, 66424, Germany

Location

Uni Hospital Marburg

Marburg, 35043, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

belinostat; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: PRS Admnistrator Gunilla Emanuelson
• Organization: Topotarget A/S

enquiries@topotarget.com

+45 39 17 83 92

Study Officials

• e-mail contact via enquiries@topotarget.com

  Valerio Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 9, 2009
• Study Start: August 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: April 1, 2012
• Last Updated: July 28, 2015
• Results First Posted: November 13, 2014

Record last verified: 2015-07

Locations

GB (1); FR (2); DE (3)