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

• ClinicalTrials.gov Identifier: NCT00893373
• Recruitment Status: Completed
• First Posted: May 6, 2009
• Last Update Posted: February 5, 2016
• Sponsor: Technische Universität Dresden
• Collaborator: Bayer
• Information provided by (Responsible Party): Technische Universität Dresden

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia (AML)	Drug: sorafenib; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 276 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: March 2009
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: September 2014

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Event-free survival [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Overall survival [ Time Frame: 36 months ]
2. Rate of complete remissions [ Time Frame: 12 weeks ]
3. Toxicity [ Time Frame: 36 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• 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

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:

SAL - Study Alliance Leukemia 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kunadt D, Stasik S, Metzeler KH, Rollig C, Schliemann C, Greif PA, Spiekermann K, Rothenberg-Thurley M, Krug U, Braess J, Kramer A, Hochhaus A, Scholl S, Hilgendorf I, Brummendorf TH, Jost E, Steffen B, Bug G, Einsele H, Gorlich D, Sauerland C, Schafer-Eckart K, Krause SW, Hanel M, Hanoun M, Kaufmann M, Wormann B, Kramer M, Sockel K, Egger-Heidrich K, Herold T, Ehninger G, Burchert A, Platzbecker U, Berdel WE, Muller-Tidow C, Hiddemann W, Serve H, Stelljes M, Baldus CD, Neubauer A, Schetelig J, Thiede C, Bornhauser M, Middeke JM, Stolzel F; A. M. L. Cooperative Group (AMLCG), Study Alliance Leukemia (SAL). Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation. J Hematol Oncol. 2022 Sep 5;15(1):126. doi: 10.1186/s13045-022-01339-8.

Rollig C, Serve H, Huttmann A, Noppeney R, Muller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Kramer A, Schafer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hanel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanss C, Repp R, Heits F, Durk H, Hase J, Klut IM, Illmer T, Bornhauser M, Schaich M, Parmentier S, Gorner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. doi: 10.1016/S1470-2045(15)00362-9. Epub 2015 Nov 6.

Herold T, Metzeler KH, Vosberg S, Hartmann L, Rollig C, Stolzel F, Schneider S, Hubmann M, Zellmeier E, Ksienzyk B, Jurinovic V, Pasalic Z, Kakadia PM, Dufour A, Graf A, Krebs S, Blum H, Sauerland MC, Buchner T, Berdel WE, Woermann BJ, Bornhauser M, Ehninger G, Mansmann U, Hiddemann W, Bohlander SK, Spiekermann K, Greif PA. Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis. Blood. 2014 Aug 21;124(8):1304-11. doi: 10.1182/blood-2013-12-540716. Epub 2014 Jun 12.

• Responsible Party: Technische Universität Dresden
• ClinicalTrials.gov Identifier: NCT00893373
• Other Study ID Numbers: TUD-SORAML-034
• First Posted: May 6, 2009
• Last Update Posted: February 5, 2016
• Last Verified: February 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Technische Universität Dresden:

AML; sorafenib

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Sorafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action