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

Conditions

Acute Myeloid Leukemia (AML)

Keywords

AML, sorafenib

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.

Christoph Röllig, Hubert Serve, Andreas Hüttmann, Richard Noppeney, Carsten Müller‐Tidow et al. (42 authors)

Blood2017-12-0721 citations

10.1182/blood.v130.suppl_1.721.721

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.

Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G, Study Alliance Leukaemia.

2015-11-06327 citations

10.1016/s1470-2045(15)00362-9

Sorafenib Versus Placebo in Addition to Standard Therapy in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia: Results from 267 Patients Treated in the Randomized Placebo-Controlled SAL-Soraml Trial

Christoph Röllig, Carsten Müller‐Tidow, Andreas Hüttmann, Richard Noppeney, Volker Kunzmann et al. (23 authors)

Blood2014-12-0648 citations

10.1182/blood.v124.21.6.6

Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis

Tobias Herold, Klaus H. Metzeler, Sebastian Vosberg, Luise Hartmann, Christoph Röllig et al. (28 authors)

Blood2014-06-13104 citations

10.1182/blood-2013-12-540716

Interventions

DRUGsorafenib

Standard AML chemotherapy plus sorafenib 400 mg BID

DRUGplacebo

Standard AML chemotherapy plus placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame
Event-free survival	36 months

Secondary

Measure	Time frame
Overall survival	36 months
Rate of complete remissions	12 weeks
Toxicity	36 months

Countries

Germany

Outcome results

None listed