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

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
sorafenib
placebo
Sponsored by
Technische Universität Dresden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring AML, sorafenib

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sozialstiftung Bamberg Klinikum am Bruderwald
  • Klinikum Bayreuth
  • Charite Campus Benjamin Franklin
  • Ev. Diakonie-Krankenhaus gGmbH Bremen
  • University Hospital Dresden
  • Klinikum Frankfurt (Oder) GmbH
  • Westpfalz-Klinikum GmbH
  • Agaplesion Diakoniekrankenhaus Rotenburg
  • Robert-Bosch-Krankenhaus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sorafenib

Placebo

Arm Description

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

Induction, Consolidation and Maintenance plus Placebo

Outcomes

Primary Outcome Measures

Event-free survival

Secondary Outcome Measures

Overall survival
Rate of complete remissions
Toxicity

Full Information

First Posted
May 4, 2009
Last Updated
February 4, 2016
Sponsor
Technische Universität Dresden
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00893373
Brief Title
Study Evaluating Sorafenib Added to Standard Primary Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Less Than 60 Years of Age
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technische Universität Dresden
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
AML, sorafenib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
276 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib
Arm Type
Experimental
Arm Description
Induction, Consolidation and Maintenance plus Sorafenib 2x 400 mg/d
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Induction, Consolidation and Maintenance plus Placebo
Intervention Type
Drug
Intervention Name(s)
sorafenib
Other Intervention Name(s)
nexavar
Intervention Description
Standard AML chemotherapy plus sorafenib 400 mg BID
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Standard AML chemotherapy plus placebo
Primary Outcome Measure Information:
Title
Event-free survival
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
36 months
Title
Rate of complete remissions
Time Frame
12 weeks
Title
Toxicity
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerhard Ehninger, Prof, MD
Organizational Affiliation
University Hospital Dresden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sozialstiftung Bamberg Klinikum am Bruderwald
City
Bamberg
ZIP/Postal Code
96049
Country
Germany
Facility Name
Klinikum Bayreuth
City
Bayreuth
ZIP/Postal Code
95445
Country
Germany
Facility Name
Charite Campus Benjamin Franklin
City
Berlin
Country
Germany
Facility Name
Ev. Diakonie-Krankenhaus gGmbH Bremen
City
Bremen
ZIP/Postal Code
28239
Country
Germany
Facility Name
University Hospital Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Klinikum Frankfurt (Oder) GmbH
City
Frankfurt (Oder)
ZIP/Postal Code
15236
Country
Germany
Facility Name
Westpfalz-Klinikum GmbH
City
Kaiserslautern
ZIP/Postal Code
67655
Country
Germany
Facility Name
Agaplesion Diakoniekrankenhaus Rotenburg
City
Rotenburg
ZIP/Postal Code
27356
Country
Germany
Facility Name
Robert-Bosch-Krankenhaus
City
Stuttgart
ZIP/Postal Code
70376
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36064577
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.
Results Reference
derived
PubMed Identifier
26549589
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.
Results Reference
derived
PubMed Identifier
24923295
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.
Results Reference
derived
Links:
URL
http://www.sal-aml.org
Description
SAL - Study Alliance Leukemia

Learn more about this trial

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

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