Study Evaluating Sorafenib Added to Standard Primary Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Less Than 60 Years of Age (SORAML)

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT00893373
First received: May 4, 2009
Last updated: February 4, 2016
Last verified: February 2016
  Purpose
Sorafenib is a multikinase inhibitor which is acting on various cellular pathways involved in the genesis of acute myeloid leukemia (AML). Sorafenib is therefore a promising candidate for improvement of chemotherapy results in AML. This clinical trial evaluates the efficacy of sorafenib added to standard chemotherapy for AML in patients between 18 and 60 years of age. Patients are randomised to receive either sorafenib capsules or placebo in addition to their chemotherapy. The placebo and the sorafenib group will be compared regarding event-free survival and other clinical outcomes. An event is either treatment failure or relapse or death. According to the study hypothesis, the sorafenib group will have less events than the placebo group.

Condition Intervention Phase
Acute Myeloid Leukemia (AML)
Drug: sorafenib
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-controlled, Randomized, Multicenter Phase-II Trial to Assess the Efficacy of Sorafenib Added to Standard Primary Therapy in Patients With Newly Diagnosed AML ≤60 Years of Age

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • Rate of complete remissions [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Enrollment: 276
Study Start Date: March 2009
Study Completion Date: September 2014
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib
Induction, Consolidation and Maintenance plus Sorafenib 2x 400 mg/d
Drug: sorafenib
Standard AML chemotherapy plus sorafenib 400 mg BID
Other Name: nexavar
Placebo Comparator: Placebo
Induction, Consolidation and Maintenance plus Placebo
Drug: placebo
Standard AML chemotherapy plus placebo

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients with newly diagnosed AML (except APL) according to the FAB and WHO classification, including AML evolving from MDS or other hematologic diseases and AML after previous cytotoxic therapy or radiation (secondary AML)
  • Bone marrow aspirate or biopsy must contain ≥ 20% blasts of all nucleated cells or differential blood count must contain ≥ 20% blasts. In AML FAB M6 ≥ 30% of nonerythroid cells in the bone marrow must be leukemic blasts. In AML defined by cytogenetic aberrations, the proportion of blasts may be < 20%.
  • Age ≥ 18 and ≤ 60 years
  • Informed consent, personally signed and dated to participate in the study
  • ECOG performance status of 0-1
  • Life expectancy of at least 12 weeks
  • Adequate liver and renal function as assessed by laboratory requirements to be conducted within 7 days prior to Screening

Exclusion criteria:

  • Patients who are not eligible for standard chemotherapy as per discretion of the treating physician
  • Central nervous system manifestation of AML
  • Cardiac disease: heart failure NYHA III or IV; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
  • Chronically impaired renal function (creatinine clearance < 30 ml/min) (Cockcroft-Gault formula)
  • Patients undergoing renal dialysis
  • Chronic pulmonary disease with relevant hypoxia
  • Known HIV and/or hepatitis C infection
  • Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
  • Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders
  • Resting blood pressure (BP) consistently higher than systolic 160 mmHg and/or diastolic 95 mmHg
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance of the protocol
  • Patients with major surgery, open biopsy or significant traumatic injury within 4 weeks of start of first dose
  • Serious, non-healing wound, ulcer or bone fracture
  • Uncontrolled active infection > Grade 2 NCI-CTC version 3.0
  • Concurrent malignancies other than AML
  • History of organ allograft
  • Allergy to study medication or excipients in study medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00893373

Locations
Germany
Sozialstiftung Bamberg Klinikum am Bruderwald
Bamberg, Germany, 96049
Klinikum Bayreuth
Bayreuth, Germany, 95445
Charite Campus Benjamin Franklin
Berlin, Germany
Ev. Diakonie-Krankenhaus gGmbH Bremen
Bremen, Germany, 28239
University Hospital Dresden
Dresden, Germany, 01307
Klinikum Frankfurt (Oder) GmbH
Frankfurt (Oder), Germany, 15236
Westpfalz-Klinikum GmbH
Kaiserslautern, Germany, 67655
Agaplesion Diakoniekrankenhaus Rotenburg
Rotenburg, Germany, 27356
Robert-Bosch-Krankenhaus
Stuttgart, Germany, 70376
Sponsors and Collaborators
Technische Universität Dresden
Bayer
Investigators
Principal Investigator: Gerhard Ehninger, Prof, MD University Hospital Dresden
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT00893373     History of Changes
Other Study ID Numbers: TUD-SORAML-034 
Study First Received: May 4, 2009
Last Updated: February 4, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Technische Universität Dresden:
AML
sorafenib

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms
Neoplasms by Histologic Type
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 30, 2016