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Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 103 AML


News
1. Overview
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms


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News


HO103

Activation Selinexor arm (01MAY2017):

 

The HOVON 103 AML study has been re-opened for inclusion of patients.

Patients will be randomized between the standard arm and the selinexor arm (initial dose level 60 mg).

Participating sites need to have a local and central approval for this arm before medication can be ordered and site can be activated.


1. Overview



Summary

A program of randomized phase II multicenter studies to assess the tolerability and efficacy of the addition of new drugs to standard induction chemotherapy in AML and high risk myelodysplasia (MDS) in patients aged ≥ 66 years


Status

open


Members

Participating groups: HOVON, SAKK



Type of study

Prospective randomized Phase II study


Echelon level

Level C-HIC


Type of monitoring for this study

Site evaluation visits


Target number of patients

200


Current number of patients

586


Date of activation

13-Apr-2010


Approved by

Selinexor (EudraCT nr: 2014-001876-75)
CCMO: NL49953.078.15 (July 18, 2016)
METC: Erasmus MC 2015-521 (October 28, 2016)
KWF: VU 2015-7726 (June 26, 2015)


Lenalidomide (EudraCTnr: 2009-013094-17):
CCMO: NL29253.078.09 (August 19, 2009)
MEC: Erasmus MC 2009-339 (April 13, 2010)
CKS: 2009-4591 (December 9, 2009)

Tosedostat (EudraCTnr: 2009-014455-68):
CCMO: NL30483.078.09 (December 28, 2009)
MEC: Erasmus MC 2010-009 (August 16, 2010)
CKS: 2009-4591 (December 9, 2009)


Study objectives

Primary objectives:
Part A (if applicable):
1. To assess the safety and tolerability of the study drug added to standard induction chemotherapy for AML(frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) and select the feasible dose level for part B of the study.
2. To assess in a randomized comparison the effect of the study drug on the CR rate.
Part B:
1. To assess the safety and tolerability of the study drug added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of the study drug.
2. To assess in a randomized comparison the effect of the in Part A selected dose of the study drug on the CR rate.

Secondary objectives:
Part B:
1. To determine the efficacy profile (event free survival (EFS), disease free survival (DFS) and overall survival (OS)) associated with the two therapy regimens.
2. To measure MRD by immunophenotyping in relation to clinical response parameters.
3. To identify potential biomarkers predictive of response, EFS, DFS and OS by exploratory genomic analysis (microarray, gene mutations).


2. Patient eligibility criteria



Inclusion criteria

Patients eligible for standard chemotherapy.
Patients 66 years and older
Patients with a diagnosis of AML and related precursor neoplasms according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or acute leukemia’s of ambiguous lineage according to WHO 2008 or a diagnosis of refractory anemia with excess of blasts (MDS) and IPSS-R > 4.5
Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
Serum creatinine ≤1.0 mg/dL (≤88.7 µmol/L); if serum creatinine >1.0 mg/dL (>88.7 µmol/L), then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where the Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine in mg/dL)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black)
NOTE: if serum creatinine is measured in µmol/L, recalculate it in mg/dL according to the equation: 1 mg/dL = 88.7 µmol/L and use the above mentioned formula.
Serum bilirubin ≤ 2.5 x upper limit of normal (ULN)
Aspartate transaminase (AST) ≤ 2.5 x ULN
Alanine transaminase (ALT) ≤ 2.5 x ULN
Alkaline phosphatase ≤ 2.5 x ULN
WHO performance status 0, 1 or 2 (see Appendix F)
Written informed consent.
Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.


Exclusion criteria

Acute promyelocytic leukemia
Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period (< 2 weeks) with Hydroxyurea is allowed
Concurrent history of active malignancy in the two past years prior to diagnosis except for:
Basal and squamous cell carcinoma of the skin
In situ carcinoma of the cervix
Blast crisis of chronic myeloid leukemia
Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera)
Cardiac dysfunction as defined by myocardial infarction within the last 6 months of study entry, or reduced left ventricular function with an ejection fraction < 50% ad measured by MUG scan or echocardiogram or unstable angina or New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix I) or unstable cardiac arrhythmias
Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance
Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.


3. Registration (& randomization) of patients



Registration

Central registration at the HOVON Data Center:
Clinical Trial Center ErasmusMC
Postbus 2040
3000 CA Rotterdam
Phone number: +31.10.7041560 (working days 9.00 - 17.00)
Fax number: +31.10.7041028
TOP address: https://www.hdc.hovon.nl/top


Registration criteria

The following information will be requested:



Protocol number
Institution name
Name of caller/responsible investigator
Sex
Date of birth
Date of diagnosis of AML or RAEB
Date written informed consent
Eligibility criteria


4. Participating parties



Principal Investigator(s)

Prof. Dr. B. Löwenberg (Erasmus MC - Centrum)
Prof. Dr. G.J. Ossenkoppele (VUMC)


Co-Investigator(s)

Dhr. Dr. D.A. Breems (ZNA Stuivenberg)


Coordinating Investigator(s)

Dr. B.T. Gjertsen (Haukeland University Hospital)
Prof. dr. J.A. Maertens (UZ Gasthuisberg)
Dr. G. Stüssi (IOSI, Ospedale Regionale)


Statistician(s)

Mw. Dr.ir. Y. van Norden (Erasmus MC - Daniel)


Central Data Manager(s)

Mw. T. van Dijk (Erasmus MC - Daniel)
Dhr. H. Hofwegen (Erasmus MC - Daniel)
Mw. N. Thuss (Erasmus MC - Daniel)


Monitor - Site Evaluation Visits

MonitorTeamCTC (Erasmus MC - Daniel)


Other functions

Central Coordinator - Molecular Diagnostics - Dhr. Dr. P. Valk (Erasmus MC - Medische Faculteit)
Central Coordinator - MRD - MRD coordination center (VUMC)
Central Coordinator - MRD - Dhr. G.J. Schuurhuis (VUMC)
Reviewer - Cytogenetics - Mw. Dr. E. van den Berg (UMCG)
Reviewer - Cytogenetics - Mw. Dr. H.B. Beverloo (Erasmus MC - Medische Faculteit)
Reviewer - HRC - HRC (Erasmus MC - Daniel)


Principal investigator

G.J. Ossenkoppele, The Netherlands (g.ossenkoppele@vumc.nl)
B. Löwenberg, The Netherlands (b.lowenberg@erasmusmc.nl)


Central data management

HOVON Data Center


5. Participating sites



Site
Included patients *
BE-Antwerpen-ZNA Middelheim
4
BE-Antwerpen-ZNA Stuivenberg
8
BE-Bruxelles-Cliniques Universitaires St. Luc
21
BE-Gent-UZ Gent
4
BE-Haine-Saint-Paul-Hopital de Jolimont
10
BE-Leuven-UZ Gasthuisberg
18
BE-Liege-Hopital de la Citadelle
10
BE-Roeselare-AZDelta
20
BE-Yvoir-Cliniques Universitaires de Mont-Godinne
13
CH-Aarau-Kantonsspital Aarau
8
Show 34 more...
* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.

6. Instruction videos



7. Download documentation / forms


 Protocol



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