NCT00893373

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
276

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Mar 2009

Longer than P75 for phase_2

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2009

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

May 4, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 6, 2009

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2011

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
Last Updated

February 5, 2016

Status Verified

February 1, 2016

Enrollment Period

2.7 years

First QC Date

May 4, 2009

Last Update Submit

February 4, 2016

Conditions

Acute Myeloid Leukemia (AML)

Keywords

AMLsorafenib

Outcome Measures

Primary Outcomes (1)

  • Event-free survival

    36 months

Secondary Outcomes (3)

  • Overall survival

    36 months

  • Rate of complete remissions

    12 weeks

  • Toxicity

    36 months

Study Arms (2)

Sorafenib

EXPERIMENTAL

Induction, Consolidation and Maintenance plus Sorafenib 2x 400 mg/d

Drug: sorafenib

Placebo

PLACEBO COMPARATOR

Induction, Consolidation and Maintenance plus Placebo

Drug: placebo

Interventions

sorafenibDRUG

Standard AML chemotherapy plus sorafenib 400 mg BID

Also known as: nexavar
Sorafenib
placeboDRUG

Standard AML chemotherapy plus placebo

Placebo

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Sozialstiftung Bamberg Klinikum am Bruderwald

Bamberg, 96049, Germany

Location

Klinikum Bayreuth

Bayreuth, 95445, Germany

Location

Charite Campus Benjamin Franklin

Berlin, Germany

Location

Ev. Diakonie-Krankenhaus gGmbH Bremen

Bremen, 28239, Germany

Location

University Hospital Dresden

Dresden, 01307, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), 15236, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, 67655, Germany

Location

Agaplesion Diakoniekrankenhaus Rotenburg

Rotenburg (Wümme), 27356, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Related Publications (3)

  • 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.

    PMID: 36064577DERIVED

  • 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.

    PMID: 26549589DERIVED

  • 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.

    PMID: 24923295DERIVED

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Gerhard Ehninger, Prof, MD

    University Hospital Dresden

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 4, 2009

First Posted

May 6, 2009

Study Start

March 1, 2009

Primary Completion

November 1, 2011

Study Completion

September 1, 2014

Last Updated

February 5, 2016

Record last verified: 2016-02

Data Sharing

IPD Sharing
Will not share

Locations

DE(9)