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

Acute Myeloid Leukemia (AML) Clinical Trial

— SORAML  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00893373
• Other study ID #: TUD-SORAML-034
• Status: Completed
• Phase: Phase 2
• First received: May 4, 2009
• Last updated: February 4, 2016
• Start date: March 2009
• Est. completion date: September 2014

Study information

• Verified date: February 2016
• Source: Technische Universität Dresden
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: September 2014
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• sorafenib
Standard AML chemotherapy plus sorafenib 400 mg BID
• placebo
Standard AML chemotherapy plus placebo

Locations

Country	Name	City	State
Germany	Sozialstiftung Bamberg Klinikum am Bruderwald	Bamberg
Germany	Klinikum Bayreuth	Bayreuth
Germany	Charite Campus Benjamin Franklin	Berlin
Germany	Ev. Diakonie-Krankenhaus gGmbH Bremen	Bremen
Germany	University Hospital Dresden	Dresden
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Agaplesion Diakoniekrankenhaus Rotenburg	Rotenburg
Germany	Robert-Bosch-Krankenhaus	Stuttgart

Sponsors (2)

Lead Sponsor	Collaborator
Technische Universität Dresden	Bayer

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		36 months	Yes
Secondary	Overall survival		36 months	Yes
Secondary	Rate of complete remissions		12 weeks	No
Secondary	Toxicity		36 months	Yes

External Links

•   SAL - Study Alliance Leukemia