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Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 102 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


HO102 news

 

Closure of study

The study is closed for further inclusion from 28SEP13 onwards.

 

New documents:

-New WMO insurance certificate for NL + BE sites is available (runs till 01DEC14) (05NOV13)

-New KWF approval document (with expansion of patient numbers) (09JUL13)

-New WMO insurance certificate for NL sites is available (runs till 01DEC13) (29JAN13)

12OCT12: New documents regarding AM9

- ICF BM sampling NL

- CA + EC approval portfolio updated

02OCT12: Updated version of the FAQ sheet

03MAY12: New CRF related documents:

- CRF (clean version as well as tracked changes version)

- DLT form

- Registration and randomisation form (no changes in content, only version date changed)

- CRF instructions (clean version as well as tracked changes version)

24APR12: New documents regarding AM7

- Protocol: clean version + tracked changes + summary of changes

- EC approvals portfolio

- CA approvals portfolio

24OCT10:New version of Pharmacy information letter (with lower maximum amount of Clofarabine kits to order).

08OCT10: New version of Pharmacy information letter (with other contact details regarding PENN).

06SEP10: New version of Pharmacy information letter (with more additions on guidelines reordering Clofarabine).

21JUL10: New version of Pharmacy information letter (with addition on guidelines reordering Clofarabine).

15JUL10: New version of the drug accountability form (only given example on page 2 has been changed).

06MAY10: NEW SAE form, because fax number on first page was incorrect, please use HO102 SAE report_06MAY10

16APR10: The Frequently Asked Questions has been updated.

08APR10: The Frequently Asked Questions has been updated.

05MRT10: The CRFs have been updated (current version 05MRT10), because of erroneous and missing information on form 16.

 

Please be aware: the dosage of Clofarabine has been reduced for investigational arm to 10 mg/m2 (as of 19NOV10)

As of 14DEC10 we have started PART B of this study.


1. Overview



Summary

Randomized study with a run-in feasibility phase to assess the added value of Clofarabine in combination with standard remission-induction chemotherapy in patients aged 18-65 years with previously untreated acute myeloid leukemia (AML) or myelodysplasia (MDS) (RAEB with IPSS >= 1.5)


Status

closed


Members

participating groups: HOVON, SAKK, Nordic group



Type of study

Prospective randomized Phase III study


Echelon level

Limited site selection


Echelon level specification

There is only a limited amount of participating sites due to budget limitations


Type of monitoring for this study

Site evaluation visits


Target number of patients

890


Current number of patients

862


Approved by

CKTO: 2009-4464-AML, approved 01-JUL-09
CCMO: NL28591.078.09 BI, approved 21-SEP-09
METC: MEC-2009-293, approved 25-JAN-10


Study objectives

Primary objectives:
Part A:
To determine the feasibility of Clofarabine when given at three possible dose levels together with standard induction cycles I and II in patients with AML/ RAEB with IPSS>=1.5 in a prospective comparison to standard induction cycles I and II without Clofarabine.
Part B:
To evaluate the effect of Clofarabine at the selected feasible dose level when combined with remission induction chemotherapy cycles I and II
as regards clinical outcome ("event-free survival") in comparison to remission induction cycles I and II with no addition of Clofarabine in a phase III study.

Secondary objectives:
Part A:
To investigate the clinical efficacy of Clofarabine in combination with remission induction chemotherapy cycles I and II with regard to complete remission rate at different dose levels of Clofarabine.
Part B:
To investigate the clinical efficacy of Clofarabine with regard to the complete remission rate, disease free survival (DFS), risk of relapse and
overall survival (OS) when combined with remission induction chemotherapy cycles I and II in all patients.
To investigate the clinical efficacy of Clofarabine when combined with remission induction chemotherapy cycles I and II in molecularly and cytogenetically distinguishable subsets with regard to the complete remission rate, disease free survival (DFS), risk of relapse and overall survival (OS).
To investigate the tolerance and toxicity of Clofarabine in combination with remission induction chemotherapy cycles I and II.
To assess the effect of Clofarabine on peripheral CD34 cell numbers for autologous peripheral blood transplantation.
To determine the prognostic value of molecular markers and gene expression profiles of the leukemia assessed at diagnosis.
To evaluate the treatment effects according minimal residual disease (MRD) measurements following therapy by standardized sampling of marrow/blood.
To evaluate the outcome of allogeneic sibling or unrelated donor SCT and autologous SCT in cytogenetically and molecularly defined and prognostic subgroups of patients.


2. Patient eligibility criteria



Inclusion criteria

Age 18-65 years, inclusive
Subjects with
* a cytopathologically confirmed diagnosis of AML according WHO classification (excluding acute promyelocytic leukaemia) or
* a diagnosis of refractory anemia with excess of blasts (RAEB) and IPSS score >=1.5 or
* patients with therapy-related AML/RAEB or
* patients with biphenotypic leukemia (Appendices A1 and A2).
Adequate renal and hepatic function tests as indicated by the following laboratory values:
* Serum creatinine <=1.0 mg/dl (<= 88.7 micromol/L); if serum creatinine >1.0 mg/dl (>88.7 micromol/L), then the 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 micromol/L, recalculate it in mg/dl according to the equation: 1 mg/dl = 88.7 micromol/L) and used above mentioned formula.
* Serum bilirubin <=1.5 × upper limit of normal (ULN)
* Aspartate transaminase (AST)/alanine transaminase (ALT) <=2.5 × ULN
* Alkaline phosphatase <= 2.5 × ULN
WHO performance status 0, 1 or 2 (see Appendix I)
Written informed consent


Exclusion criteria

Acute promyelocytic leukaemia
Previous treatment for AML or RAEB, except hydroxyurea
Concurrent history 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 MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable), or
* Unstable angina, or
* Unstable cardiac arrhythmias
Pregnant or lactating females
Unwilling or not capable to use effective means of birth control


3. Registration (& randomization) of patients



Registration

Central registration at the HOVON Data Center:
Erasmus MC Cancer Institute, Clinical Trial Center (Hs-423)
P.O. Box 2040
NL-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)


Coordinating Investigator(s)

Dr. E. Laane (North Estonia Medical Centre)
Prof. dr. J.A. Maertens (UZ Gasthuisberg)
Dr. T. Pabst (Inselspital)


Statistician(s)

Mw. Dr.ir. Y. van Norden (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 - Special Investigations - Mw. Dr. M. Jongen-Lavrencic (Erasmus MC - Daniel)
Central Coordinator - Special Investigations - Dhr. G.J. Schuurhuis (VUMC)
Central Coordinator - Special Investigations - Dhr. Dr. P. Valk (Erasmus MC - Medische Faculteit)
Reviewer - Cytogenetics - Mw. Dr. H.B. Beverloo (Erasmus MC - Medische Faculteit)
Reviewer - Cytogenetics - Dhr. Dr. C.H.M. Mellink (AMC)
Reviewer - Cytogenetics - Dhr. Dr. P.J. Poddighe (VUMC)
Reviewer - HRC - Mw. T. de Jong (Erasmus MC - Daniel)


5. Participating sites



Site
Included patients *
BE-Antwerpen-ZNA Middelheim
6
BE-Antwerpen-ZNA Stuivenberg
10
BE-Bruxelles-Cliniques Universitaires St. Luc
22
BE-Gent-UZ Gent
11
BE-Haine-Saint-Paul-Hopital de Jolimont
9
BE-Leuven-UZ Gasthuisberg
48
BE-Liege-Hopital de la Citadelle
18
BE-Montigny-le-Tilleul-CHU de Charleroi-Vesale
3
BE-Roeselare-AZDelta
8
BE-Wilrijk-Sint Augustinus
1
Show 35 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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