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Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 132 AML / SAKK


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


HO132 news

27JAN16: Amendment 06 approved by EC Netherlands. Please send in requested forms (site documents checklist, ICFs + protocol signature page).

29JAN15: Amendment 03 approved by EC Belgium. Please send in requested forms (site documents checklist + ICFs + Protocol Signature page) when you wish to be activated

Amendment 03 approved in BE on 28JAN15.

28JAN15: Amendment 03 implemented in TOP. Please send in requested forms (site documents checklist + ICFs + Protocol Signature Page) when you wish to be activated.

Amendment 03 approved in NL on 23JAN15.

 

New documents:

24OKT16: New labmanual available for all sites (13OKT16)

27JAN16: All mentioned documents are updated in relation to AM06 approval

 - CA and EC approval portfolio

 - Protocol (clean and tracked changes version + summary of changes)

 - ICFs (pre-study sampling + main ICF versions in clean and tracked changes + summary of changes)

 - Second Randomization form

 - Pregnancy Prevention Program

 - Chemo schedules

14JAN16: New CRF instructions are available

18NOV15: New Pharmacy info letter available with updated contact information + updated training powerpoint for IDOS

30SEP15: New FAQ document available with updated questions and answers

14SEP15: New FAQ document available with updated questions and answers

17JUN15: New labmanual available (updated version for samples regarding relapse)

28MAY15: New FAQ document available with updated questions and answers

28MAR15: New labmanual available for all sites that reflects AM03 changes

26JAN15: All mentioned documents are updated in relation to AM03 approval

 - CA and EC approval portfolio

 - Protocol (clean and tracked changes version + summary of changes)

 - ICFs (all versions in clean and tracked changes + summary of changes)

 - ITF content (zip file updated)

 - CRFs updated + instructions

 - NoteToFile for stop usage Patient Diary

 - SAE report form and instructions

 - Lab manual

 - FAQ sheet

14AUG14: Flow schema + cyto schema cycle 1 and 2.

09JUL14: SAE forms + instructions have been updated.

24APR14: The Frequently Asked Questions has been updated.

28MAY15: New FAQ document available with updated questions and answers

1. Overview



Summary

Randomized study with a run-in dose-selection phase to assess the added value of lenalidomide in combination with standard remission-induction chemotherapy and post-remission treatment in patients aged 18-65 years with previously untreated acute myeloid leukemia (AML) or high risk myelodysplasia (MDS) (IPSS-R risk score > 4.5)


Status

open


Members

Participating groups: HOVON, SAKK, AGMT, Nordic, Swedish group



Type of study

Prospective randomized Phase III study


Echelon level

Limited site selection


Echelon level specification

There is only a limited amount of sites due to financial reasons


Type of monitoring for this study

Site evaluation visits


Target number of patients

927


Current number of patients

881


Date of activation

25-Mar-2014


Approved by

BE METC: 20FEB14
BE CA: 12FEB14
NL METC: 25MAR14
NL CA: 13NOV14
LU METC: 08MAY14
LU CA: 03JUN14
NO METC: 24JUN14
NO CA: 10SEP14
LT METC: 15JUL14
LT CA: 28AUG14
SE METC: 13AUG14
SE CA: 25AUG14
CH METC: 23DEC14
CH CA: 14AUG14


Change history / amendement

AM01 (BE): Change documents due to required changes of NL parallel submission
AM02 (BE): Addition of Belgium site
AM03 (ALL): Change of dose level as requested by DSMB
AM06 (ALL): clarification of inclusion criteria, increase nr of patients, addition of criteria for inclusion 2nd randomization


Study objectives

Primary objectives:

Part A-run-in:
To select in a randomized approach the feasible dose level of lenalidomide when given orally at three variable dose levels (20 mg/ day 1-21; 30 mg/ day 1-21 and 40 mg/ day 1-21 ) in combination with standard induction cycles I and II in patients with AML/ MDS with IPSS-R > 4.5

Part A:
To evaluate the effect of lenalidomide on EFS at the (during Part A run-in) selected feasible dose level when combined with remission induction chemotherapy cycles I and II in a randomized comparison to remission induction cycles I and II without addition of lenalidomide in a phase III study

Part B:
To evaluate the effect on the Cumulative incidence of relapse (CIR) of 6 cycles of maintenance therapy with lenalidomide treatment (10 mg/day for 21 days followed by 14 days rest) after post remission chemotherapy cycle III or autoHSCT versus observation only


2. Patient eligibility criteria



Inclusion criteria

Registration/Randomization 1:
Age 18-65 years, inclusive
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 score > 4.5
WHO performance status 0, 1 or 2
Sampled bone marrow and/ blood cells for centralized molecular analysis and MRD evaluation. Unless in case of a dry tap with no possibility to collect marrow cells; in that case only blood cells to be sampled, or in case of patient refusal.
Adequate renal and hepatic functions 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/1.73m2 as calculated by the Modification of Diet in Renal Disease equation where 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 umol/L, recalculate it in mg/dL according to the equation: 1 mg/dL = 88.7 umol/L) and use 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
Written informed consent
Ability to adhere to the lenalidomide Pregnancy Prevention Program

Registration/Randomization 2a (Part B):
CR or CRi
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
Platelet count ≥ 75 x 10^9/L
Serum creatinine clearance ≥ 30 ml/min or estimated glomerular filtration rate (GFR) > 60 mL/min/1.73m^2
Total bilirubin ≤ 2.5 x ULN
AST ≤ 2.5 x ULN
ALT ≤ 2.5 x ULN


Exclusion criteria

Registration/Randomization 1:
Previous treatment with Lenalidomide
Acute promyelocytic leukemia
Myeloproliferative neoplasia
Previous treatment for AML or high risk MDS (IPSS-R > 4.5), except hydroxyurea
Concurrent history of active malignancy in two past years prior to diagnosis except for:
- basal and squamous cell carcinoma of the skin
- in situ carcinoma of the cervix
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% as measured by MUG scan or echocardiogram or
- Unstable angina, or
- Unstable cardiac arrhythmias
Hypersensitivity to the active substance or to any of the excipients of the drug product
Pregnant or lactating females
Unwilling or not capable to use effective means of birth control
Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Registration/Randomization 2a (Part B):
Severe cardiac dysfunction (NYHA classification II-IV)
Severe pulmonary dysfunction (CTCAE grade III-IV)
Severe neurological or psychiatric disease
Serious active infections
Previous serious toxicities related to the use of lenalidomide
CMV reactivation, which is not responsive to first line valganciclovir


3. Registration (& randomization) of patients



Registration

Central registration at the HOVON Data Center:
Erasmus MC - Clinical Trial Center
Postbus 2040
3000 CA Rotterdam
Phone number: +31 10 7041560 (working days 9.00-17.00)
Fax nuber: +31 10 7041028
TOP address: href="https://www.hdc.hovon.nl/top">http://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 written informed consent
Specific items patient gives consent for (see ICF)
Eligibility criteria
Stratification factors


4. Participating parties



Principal Investigator(s)

Prof. Dr. B. Löwenberg (Erasmus MC - Centrum)


Co-Investigator(s)

Dhr. Dr. D.A. Breems (ZNA Stuivenberg)
Dr. N. Fischer (Krankenhaus Munchen-Schwabing)
Mr.Dr. B.T. Gjertsen (Haukeland University Hospital)
Dr. H. Hallbook (Uppsala Akademiska Sjukhuset)
Dr. S. Lehmann (Karolinska UH loc. Solna)
Dr. M. Manz (Universitätsspital)
Prof. Dr. G.J. Ossenkoppele (VUMC)
Dhr. Dr. K.L. Wu (ZNA Stuivenberg)


Coordinating Investigator(s)

Dr. T. Fischer (Universitaetsklinikum Magdeburg)
Y. Floisand (Oslo Universitetssykehus)
Prof.Dr. R. Greil (SALK Salzburg)
Prof. Dr. L. Griskevicius (Vilnius University Hospital Santariskiu)
Dr.med. F. Heidel (Universitaetsklinikum Magdeburg)
Dr. M. Höglund (Uppsala Akademiska Sjukhuset)
Dr. E. Laane (North Estonia Medical Centre)
Prof. dr. J.A. Maertens (UZ Gasthuisberg)
Dr. T. Pabst (Inselspital)
Dr. L. Plawny (Centre Hospitalier de Luxembourg)
Prof. Dr. K. Porkka (Central UH of Helsinki)


Statistician(s)

Ms. P. Gradowska (Erasmus MC - Daniel)


Central Data Manager(s)

Mw. T. van Dijk (Erasmus MC - Daniel)
Mw. S. Jansen - van den Bergh (Erasmus MC - Daniel)
Mw. M. Vania (Erasmus MC - Daniel)


Monitor - Site Evaluation Visits

N. Hurni (SAKK)
Mw. J. Kloezeman (Erasmus MC - Daniel)
Mw. T. van de Klundert (Erasmus MC - Daniel)


Other functions

Central Coordinator - Molecular Diagnostics - HO132_MolDiag (Erasmus MC - Medische Faculteit)
Central Coordinator - MRD - Dhr. Dr. E. Braakman (Erasmus MC - Medische Faculteit)
Central Coordinator - MRD - Flowcytometry.diagnostics (Erasmus MC - Centrum)
Central Coordinator - MRD - hematocytologie (Erasmus MC - Centrum)
Central Coordinator - MRD - integrale.diagnostiek (Erasmus MC - Centrum)
Central Coordinator - MRD - Mw. dr. M. Jongen-Lavrencic (Erasmus MC - Daniel)
Central Coordinator - MRD - Mw. Dr. K. van Lom (Erasmus MC - Centrum)
Central Coordinator - MRD - MRD coordination center (VUMC)
Central Coordinator - MRD - Dhr. Dr. P. Valk (Erasmus MC - Medische Faculteit)
Central Coordinator - MRD - Dhr. Dr. V.H.J. van der Velden (Erasmus MC - Centrum)
Reviewer - HRC - HRC (Erasmus MC - Daniel)
Reviewer - HRC - Mw. T. de Jong (Erasmus MC - Daniel)


Principal investigator

Principal Investigator: B. Löwenberg (b.lowenberg@erasmusmc.nl)
Co-investigator: G. Ossenkoppele (g.ossenkoppele@vumc.nl)


Coordinating investigator(s)

R. Greil (AT)
J. Maertens (BE)
T. Pabst (CH)
T. Fischer (DE)
H. Everaus (EE)
Y. Floisand (FI)
L. Griskevicius(LT)
L. Plawny (LU)
B.T.Gjertsen (NO)
M. Höglund (SE)


Trial manager

R.L.J. Roach (r.roach@erasmusmc.nl)


Central data management

A. Verbrugge (a.verbrugge.1@erasmusmc.nl)


5. Participating sites



Site
Included patients *
BE-Antwerpen-ZNA Stuivenberg
12
BE-Antwerpen Edegem-Universitair Ziekenhuis Antwerpen
17
BE-Bruxelles-Cliniques Universitaires St. Luc
24
BE-Gent-UZ Gent
11
BE-Haine-Saint-Paul-Hopital de Jolimont
5
BE-Leuven-UZ Gasthuisberg
35
BE-Liege-Hopital de la Citadelle
7
BE-Mons-CHU Ambroise Pare
0
BE-Roeselare-AZDelta
22
BE-Wilrijk-Sint Augustinus
0
Show 42 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

 Patient Information & IC form (NL)



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