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Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 42 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


HO 42 news

The HO42 AML study has been published in the New England Journal of Medicine. This resulted in a lot of media attention, please find a selection of the publications here.


1. Overview



Summary

Randomized induction and post induction therapy in adult patients (<= 60 yrs of age) with acute myelocytic leukemia (AML) or refractory anemia with excess of blasts (RAEB, RAEB-t) with IPSS score >= 1.5


Status

closed



Type of study

Prospective randomized Phase III study


Target number of patients

800


Date of activation

02-Jan-2001


Date closed

01-Feb-2006


Approved by

CKVO: CKVO 2000-08
MEC: METC EUR/AZR, 29 November 2000


Change history / amendement

Amendment 1: 27 June 2001
Amendment 2: 27 November 2001, Activated 14 January 2002
Amendment 3: 23 September 2003, Activated 20 October 2003
Amendment 4: 1 July 2004


Study objectives

To study in a randomized comparison the two different dose levels of cytarabine during induction cycles I and II as regards the complete remission rate, disease free survival and overall survival.
To evaluate by randomization the therapeutic effect of marrow ablative chemotherapy in adjunct to peripheral blood stem cell transplantation (PBSCT) in patients with intermediate and poor risk AML in CR (probability of relapse more than 50%) in comparison to intensive post-remission chemotherapy
To evaluate the outcome of allogeneic sibling SCT in intermediate risk patients and compare the results with those after chemotherapy and ablation + PBSCT
To assess the value of early allogeneic family donor and unrelated donor SCT in patients with poor risk AML in comparison to the results in those treated with chemotherapy and ablation + PBSCT


2. Patient eligibility criteria



Inclusion criteria

Age 18-60 years (incl.)
Subjects with a cytopathologically confirmed diagnosis of
(a) AML (M0-M2 and M4-M7, FAB classification, appendix A), or
(b) with refractory anemia with excess of blasts (RAEB) or refractory anemia with excess of blasts in transformation (RAEB-t) with an IPSS score of >= 1.5 (appendix B)
Patients with therapy-related AML/RAEB/RAEB-t are eligible provided they have not received chemotherapy during the past 6 months. Also patients with biphenotypic leukemia may be included.
Subjects with a secondary AML progressing from antecedent myelodysplasia are eligible. Antecedent MDS refers to a condition of at least 4 month duration
WHO performance status < 3 (see appendix E)
Written informed consent

Eligibility criteria for second randomization for post remission therapy:
In complete remission (Appendix C)
Peripheral blood recovery
Intermediate or poor risk status according to criteria of appendix G
Not planned for or not eligible for genotypically matched allogeneic SCT (intermediate-risk/high-risk patients) or unrelated HLA matched SCT (high risk patients)
Absence of congestive heart failure (i.e., ejection fraction greater than 50% as assessed by MUGA scan or echocardiogram)
Absence of severe pulmonary disease
No active uncontrolled infection
Serum bilirubin as a parameter of liver function abnormalities not elevated above 3x normal value
Number of blood cells collected (“transplant”; PBSCT) being at least 10 x 104 CFU-GM per kg or 2 x 106 CD34-positive cells per kg. In case of no or insufficient PBSCT, an adequate autologous marrow graft must have been collected
Performance status of WHO grade 0, 1 or 2 at time of randomization
Informed consent


Exclusion criteria

Prior chemotherapy within 6 months of study entry
Relapse of AML or MDS after induction chemotherapy
Prior stem cell transplant
Previous polycythemia rubra vera
Primary myelofibrosis
Blast crisis of chronic myeloid leukemia
AML-FAB type M3 or AML with cytogenetic abnormality t(15;17) or AML with a PML/RAR alpha or a variant RAR alpha fusion gene
Impaired hepatic or renal function as defined by:
a. ALT and/or AST > 3 x normal value
b. Bilirubin > 3 x normal value
c. Serum creatinin > 3 x normal value (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, etc.)
Cardiac dysfunction as defined by:
a. Myocardial infarction within the last 6 months of study entry, or
b. Reduced left ventricular function with an ejection fraction <50% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable)
c. Unstable angina
d. Unstable cardiac arrhythmias
Pregnancy


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:



Name institute
Name of caller/physician who treats the patient
Patient’s initials or code
Patient’s hospital record number
Sex
Date of birth
Date of diagnosis of AML or RAEB or RAEB-t
WHO performance status
White blood cell count (WBC)
FAB type of AML or RAEB or RAEB-t
Eligibility criteria
Prior hematological or oncological disease
Previous chemotherapy or radiotherapy

For the second randomisation the following information is required:
Protocol number
Name institute
Name of caller/responsible investigator
Patient's study number
Response after cycle I (CR or no CR)
Eligibility criteria


4. Participating parties



Principal investigator

B Lowenberg (b.lowenberg@erasmusmc.nl)


Coordinating investigator(s)

M.A. Boogaerts
E. Vellenga
T. Kovacsovics


Statistician(s)

W.L.J. van Putten (w.vanputten@erasmusmc.nl)


Central data management

L. el Jarari (l.eljarari@erasmusmc.nl)
S. Ramnarain (s.ramnarain@erasmusmc.nl)


Other functions

Central Cytogeneticist:
A. Nieuwint
M. van den Blij-Philipsen


5. Participating sites



6. Instruction videos



7. Download documentation / forms


 Protocol



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