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Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 92 AML / SAKK


News
1. Overview
Study details
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


HO92 news

HOVON 92 AML / SAKK 30/08: please note, the study has been closed. 

 

  

Activated hospitals:
- Haukeland - Bergen [N] (07DEC09)
- MST - Enschede (10NOV09)
- CHR - Liege[B] (30SEPT09)
- USZ - Zürich[CH] (30SEPT09)
- CHUG - Geneva[CH] (28AUG09)
- UZG - Leuven[B] (28AUG09)
- KSA - Aarau[CH] (20AUG09)
- HH - Roeselare[B] (17AUG09)
- MeanderMC (14AUG09)
- ZNA Stuivenberg - Antwerp[B] (14AUG09)
- Mont Godinne -Yvoir[B] (14AUG09)
- St Luc - Brussel[B] (12AUG09)
- Jolimont - Haine[B] (12AUG09)
- UMCU (10AUG09)
- KSL - Luzern[CH] (17JUL09)
- UHBS - Basel[CH] (17JUN09)
- CHUV - Lausanne[CH] (12JUN09)
- OLVG (29APR09)
- Inselspital - Bern[CH] (02APR09)
- MCL (20MAR09)
- MUMC (19MAR09)
- Haga Ziekenhuis (17MAR09)
- Isala Klinieken (29JAN09)
- Antonius (26JAN09)
- VUMC (16JAN09)
- AMC (02DEC08)
- ErasmusMC (04NOV08)

 

Updated documents (in reversed chronological order of date replacement):

- New CRF version of 10 March 2009. Changes: addition on DLT form and PDF correct conversion of symbols.

- PI & ICF amendment(s) new version that clearifies the fact that there were two versions of Part A and Part B submitted to the cMETC.

- Amendment 1 replacements/additions:

  - Protocol (now version 02dec08)

  - Protocol amendment(s)

  - CRFs (now version 30jan09)

  - CRF instructions (now version 24feb09)

  - PI & ICF amendment(s)

  - MEC approval (d.d. 27feb09)

  - Signature page of protocol

  - Registration (&randomization) form (now version 30jan09)

  - HO92PIF_part A_AM1_30jan09

  - HO92PIF_partB_AM1_30jan09

  - HO92PIF_PK_AM1_02dec08

  - DLT form_30jan09

- Instructions for laboratory investigations HO92_Instructions for laboratory investigations_v04MAR09 has been updated to give clearer information.

- Statement of expenses form for NLsites HO92_declarationform_NLsites_v03MAR09 has been updated.

- Document named HO92_Questions_and_Answers_v28jan09 has been updated.

- Document named ho92_vpk_werkdocument_general_v06nov08 has been updated.

- Document named HO92_Questions_and_Answers_v23jan09 has been updated.

- CKTO approval has been received, the document can be found below "forms for local submission"

- ho92_pk_vpk_werkdocument_general_v07nov08 instead of version dd28OCT08 which had incorrect data on sheet regarding Arm B bloodsamples.

- MEC Correspondence has been replaced by a new version. New version also includes email send by cMETC on 28AUG08 and response by PI dd 03SEP08.

 

 

 


1. Overview



Summary

Randomized study to assess the added value of Laromustine 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



Study details



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

Study specific


Target number of patients

800


Approved by

EudraCTnr.: 2008-000404-92
CKTO: 2008-4249, 25 nov 08
MEC: METC EMC, 2008-216, 12 sept 08


Study objectives

Primary objectives
Part A: To determine the feasibility of Laromustine 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 Laromustine
Part B: To evaluate the effect of Laromustine 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 Laromustine in a phase III study

Secondary objectives
Part A:
To evaluate the pharmacokinetics of Laromustine in the combination with cytarabine-idarubicin remission induction chemotherapy in a selection of patients at different dose levels of Laromustine as well as in a limited number of controls
To investigate the clinical efficacy of Laromustine in combination with remission induction chemotherapy cycles I and II with regard to complete remission rate at different dose levels of Laromustine
Part B:
To investigate the clinical efficacy of Laromustine 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 Laromustine 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 Laromustine in combination with remission induction chemotherapy cycles I and II
To evaluate the pharmacokinetics of Laromustine and cytarabine-idarubicine remission induction chemotherapy in a limited number of patients in both treatment arms
To assess the effect of Laromustine 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).
WHO performance status 0, 1 or 2 (see Appendix I)
Written informed consent


Exclusion criteria

During part A of the study patients with a good risk AML, if already known at randomisation, will be excluded from randomisation and will be treated according to the control arm.
Acute promyelocytic leukaemia
Previous treatment for AML or RAEB, except hydroxyurea
Impaired hepatic or renal function as defined by:
- ALT and/or AST > 3 x Upper Limit of Normal (ULN), or
- Bilirubin > 3 x ULN, or
- Serum creatinine> 3 x ULN (after adequate hydration), unless these are most likely caused by AML organ infiltration,
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
Disulfiram (Antabuse) and metronidazol (Flagyl) discontinued 24 hours prior to study treatment.
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...: http://www.hdc.hovon.nl/top


Registration criteria

The following information will be requested:



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


4. Participating parties



Principal investigator

B. Lowenberg (b.lowenberg@erasmusmc.nl)
G. Ossenkoppele (g.ossenkoppele@vumc.nl)


Coordinating investigator(s)

J. Maertens (B)
T. Pabst (CH)


Statistician(s)

F. Termorshuizen (f.termorshuizen@erasmusmc.nl)


Trial manager

P. Cornelisse (p.cornelisse@erasmusmc.nl)


Central data management

Sonia Cunha (s.cunha@erasmusmc.nl)
Martin Sterrenberg (m.sterrenberg.1@erasmusmc.nl)
Nicole Thuss (n.thuss@erasmusmc.nl)
Tamara van Dijk (t.m.r.vandijk@erasmusmc.nl)
Petra Cornelisse (p.cornelisse@erasmusmc.nl)


5. Participating sites



6. Instruction videos



7. Download documentation / forms


 Protocol



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