Clinical trial NCT00893373: Study Evaluating Sorafenib Added to Standard Primary Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Less Than 60 Years of Age
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: AML
sorafenib
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2009-05-06
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Event-free survival
timeFrame: 36 months
Secondary outcomes:
measure: Overall survival
timeFrame: 36 months
measure: Rate of complete remissions
timeFrame: 12 weeks
measure: Toxicity
timeFrame: 36 months
Other outcomes:
Locations:
city: Bamberg
country: Germany
facility: Sozialstiftung Bamberg Klinikum am Bruderwald
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin
city: Bremen
country: Germany
facility: Ev. Diakonie-Krankenhaus gGmbH Bremen
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Rotenburg
country: Germany
facility: Agaplesion Diakoniekrankenhaus Rotenburg
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
Study officials:
affiliation: University Hospital Dresden
name: Gerhard Ehninger, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.