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Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 135 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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1. Overview



Summary

A program of randomized phase II multicenter studies to assess the tolerability and efficacy of the addition of new drugs to 10-day decitabine in UNFIT (i.e. HCT-CI ≥ 3) AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) patients aged >= 66 years.


Status

planned


Members

Participating groups; HOVON, SAKK



Type of study

Prospective randomized Phase II study


Echelon level

Limited site selection


Type of monitoring for this study

Site evaluation visits


Target number of patients

140


Current number of patients

69


Date of activation

07-Sep-2016


Approved by

The Netherlands:
EC UMCG; 18MAR2016
CA CCMO; 30NOV2015
KWF; 18DEC2015


Study objectives

Primary objectives
To assess in a randomized comparison the effect of ibrutinib added to 10-day decitabine treatment on the cumulative CR/CRi rate after 3 cycles.

Secondary objectives
To assess the safety and tolerability of Ibrutinib added to 10-day decitabine treatment for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of the study.
To determine the efficacy profile: response rate (CR, CRi, PR), event free survival (EFS) and overall survival (OS) associated with the two therapy regimens.
To determine the impact of 3 days ibrutinib monotherapy (pre-treatment) on WBC count, circulating blast count, and translational endpoints (mass cytometry).
To measure MRD by immunophenotyping and PCR in relation to clinical response parameters.
To identify potential biomarkers predictive of response, EFS and OS by exploratory analysis (gene mutations, kinome, methylome).
To evaluate the prognostic value of baseline physical and functional conditions using comprehensive geriatric assessment tools (short physical performance battery (SPPB) and activities of daily living (ADL) on treatment outcome).


2. Patient eligibility criteria



Inclusion criteria

♦ 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
♦ Patients 66 years and older.
♦ Patients NOT eligible for standard chemotherapy, defined as HCT-CI ≥ 3. (Appendix G) or Patient NOT eligible for standard chemotherapy for other reasons (wish of patient).
♦ WBC ≤ 30 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start decitabine treatment)
♦ Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
Serum creatinine ≤ 2.5 mg/dL (≤ 221.7 μmol/L), unless considered AML-related
Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert’s syndrome
Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related
♦ WHO performance status 0, 1 or 2
♦ Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
♦ Written informed consent.
♦ Patient is capable of giving informed consent.


Exclusion criteria

♦ Acute promyelocytic leukemia.
♦ Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed
♦ Diagnosis of any previous or concomitant malignancy is an exclusion criterion: except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization.
♦ Blast crisis of chronic myeloid leukemia.
♦ Inability to discontinue any anti-coagulants (including ascal)
♦ Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
♦ Cardiac dysfunction as defined by:
Myocardial infarction within the last 3 months of study entry, or
Reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram or
Unstable angina or
New York Heart Association (NYHA) grade IV congestive heart failure (see Appendix I) or
Unstable cardiac arrhythmias
♦ Patient has had major surgery within the past 4 weeks or a major wound that has not fully healed.
♦ Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.
♦ History of stroke or intracranial hemorrhage within 6 months prior to randomization.
♦ Patient has a history of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B.
♦ Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
♦ 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 hydroxyurea
♦ Any psychological, familial, sociological or 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:

TOP address: https://www.hdc.hovon.nl/top

Phone number: +31.10.7041560
(working days 9.00 - 17.00)
Fax number: +31.10.7041028

Clinical Trial Center
Erasmus MC Cancer Institute
Postbus 2040
3000 CA Rotterdam


Registration criteria

The following information will be requested:



Protocol number
Institution name
Name of caller/responsible investigator
Sex
Date of birth or partial date of birth, e.g. year of birth
Age at date of inclusion
Date written informed consent
Specific items patient gives consent for (see ICF)
Eligibility criteria
Stratification factors


4. Participating parties



Principal Investigator(s)

Prof. G. Huls (UMCG)


Co-Investigator(s)

Ms. V. Havelange (Cliniques Universitaires St. Luc)
Prof. Dr. B. Löwenberg (Erasmus MC - Centrum)
Prof. Dr. G.J. Ossenkoppele (VUMC)


Coordinating Investigator(s)

Ms. S. Blum (Centre Hospitalier Univ. Vaudois)
Dhr. Dr. D.A. Breems (ZNA Stuivenberg)
Dr. B.T. Gjertsen (Haukeland University Hospital)
Prof. Dr. L. Griskevicius (Vilnius University Hospital Santariskiu)


Statistician(s)

Mw. Dr.ir D. Chitu (Erasmus MC - Daniel)


Monitor - Site Evaluation Visits

Mw. W.M Keller (Erasmus MC - Daniel)
Mw. J. Kloezeman (Erasmus MC - Daniel)
Mw. T. van de Klundert (Erasmus MC - Daniel)


Other functions

Central Coordinator - Molecular Diagnostics - HO135_MolDiag (Erasmus MC - Medische Faculteit)
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. H.B. Beverloo (Erasmus MC - Medische Faculteit)
Reviewer - HRC - HRC (Erasmus MC - Daniel)
Reviewer - HRC - Mw. Dr. M. Jongen-Lavrencic (Erasmus MC - Daniel)


Principal investigator

Dr. G. Huls (UMCG)


Trial manager

Marleen Luten (m.luten@erasmusmc.nl)


Central data management

René Hollestein (r.hollestein@erasmusmc.nl)


5. Participating sites



Site
Included patients *
BE-Antwerpen-ZNA Stuivenberg
4
BE-Roeselare-AZDelta
1
CH-Aarau-Kantonsspital Aarau
1
CH-Basel-University Hospital Basel
0
CH-Bellinzona-IOSI, Ospedale Regionale
8
CH-Bern-Inselspital
11
CH-Fribourg-HFR Hopital Cantonal
0
CH-Geneve (14)-Hôpital Cantonal Universitaire
2
CH-Lausanne-Centre Hospitalier Univ. Vaudois
0
CH-Luzern-Kantonsspital Luzern
1
Show 20 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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