AML-AZA: Efficacy of 5-azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Sponsor

University Hospital Muenster (Other)

Overall Status

Completed

CT.gov ID

NCT00915252

Collaborator

Celgene Corporation (Industry), Amgen (Industry)

214

Enrollment

Locations

Arms

Duration (Months)

7.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of the study is to determine, whether the addition of 5-azacytidine to standard chemotherapy in elderly patients with newly diagnosed AML improves treatment results (event free survival).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: azacitidine Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

214 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Multi-center Phase II Trial to Assess the Efficacy of 5-azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5-azacytidine Patients enrolled in this arm will receive standard induction and consolidation chemotherapy preceded by 5-azacytidine. These patients will additionally receive maintenance therapy with 5-azacytidine for one year after start of induction therapy.	Drug: azacitidine Starting dose has been determined during run-in dose finding part of the study. Starting dose of the interventional drug is 75 mg/m²/d. Application form: During induction therapy phase: i.v. on days -5--1 before standard chemotherapy for 1 or 2 cycles, During consolidation therapy: s.c. on days -5--1 before standard chemotherapy (2 cycles). During maintenance therapy: s.c. on days 1-5 on a 28day cycle till maximum one year after start of first induction therapy. Other Names: 5-azacytidine Vidaza
Active Comparator: standard chemotherapy Patients enrolled in this arm will receive standard chemotherapy treatment.	Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine Induction therapy: Daunorubicin 60mg/m²/d i.v.on days 3,4,5 AraC 100mg/m²/d i.v. on days 1-7 Consolidation therapy: AraC 1g/m² twice a day on day 1,3,5 Other Names: Ara-C Daunoblastin DaunoXome Alexan Ara-cell Udicil

Arm

Intervention/Treatment

Experimental: 5-azacytidine

Patients enrolled in this arm will receive standard induction and consolidation chemotherapy preceded by 5-azacytidine. These patients will additionally receive maintenance therapy with 5-azacytidine for one year after start of induction therapy.

Drug: azacitidine

Starting dose has been determined during run-in dose finding part of the study. Starting dose of the interventional drug is 75 mg/m²/d. Application form: During induction therapy phase: i.v. on days -5--1 before standard chemotherapy for 1 or 2 cycles, During consolidation therapy: s.c. on days -5--1 before standard chemotherapy (2 cycles). During maintenance therapy: s.c. on days 1-5 on a 28day cycle till maximum one year after start of first induction therapy.

Other Names:

5-azacytidine

Vidaza

Active Comparator: standard chemotherapy

Patients enrolled in this arm will receive standard chemotherapy treatment.

Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine

Induction therapy: Daunorubicin 60mg/m²/d i.v.on days 3,4,5 AraC 100mg/m²/d i.v. on days 1-7 Consolidation therapy: AraC 1g/m² twice a day on day 1,3,5

Other Names:

Ara-C

Daunoblastin

DaunoXome

Alexan

Ara-cell

Udicil

Outcome Measures

Primary Outcome Measures

Median Event Free Survival (EFS) of all AML patients [continously up to 12 months after start of study]

Secondary Outcome Measures

Median event free survival of AML patients with different cytogenetic and molecular risk groups [continously up to 12 months after study start]
Median overall survival of all AML patients [continously up to 12 month after start of study]
Median overall survival of AML patients with different cytogenetic and molecular risk groups [continously up to 12 month after start of study]
Relapse free survival [continously up to 12 months after start of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with newly diagnosed AML (except APL) according to the FAB or WHO classification, including AML evolving from MDS or other hematological diseases and AML after previous cytotoxic therapy or radiation (secondary AML).
Bone marrow aspirate or biopsy must contain ≥ 20% blasts of all nucleated cells or differential blood count must contain ≥ 20% blasts. In AML FAB M6 ≥ 30% of non-erythroid cells in the bone marrow must be leukemic blasts. In AML defined by cytogenetic aberrations the proportion of blasts may be < 20%.
Age ≥ 61 years
Informed consent, personally signed and dated to participate in the study
Male patients enrolled in this trial must use adequate barrier birth control measures during the course of the 5-azacytidine treatment and for at least 3 months after the last administration of 5-azacytidine.

Exclusion Criteria:

Patients who are not eligible for standard chemotherapy as described in chapter 5.2 and 5.3
Hyperleukocytosis (leukocytes > 20,000/µl) at study entry. These patients should be treated with hydroxyurea or receive leukocytapheresis treatment (if leukocytes > 100,000/µl) according to routine practice and entered into the study when leukocyte counts below 20,000/µl are reached. This applies only for the controlled part of the study.
Patients with initial hyperleukocytosis above 20,000/µl can only be enrolled into the controlled part of the study, but not in the run-in dose finding part.
Known central nervous system manifestation of AML
Cardiac Disease: Heart failure NYHA class 3 or 4; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
Chronically impaired renal function (creatinin clearance < 30 ml / min)
Inadequate liver function (ALT and AST ≥ 2.5 x ULN) if not caused by leukemic infiltration
Total bilirubin ≥ 1.5 x ULN if not caused by leukemic infiltration
Known HIV and/or hepatitis C infection
Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders
Uncontrolled active infection
Concurrent malignancies other than AML with an estimated life expectancy of less than two years
History of organ allograft
Hypersensitivity to cytarabine (not including drug fever or exanthema), daunorubicin, azacytidine or mannitol
Previous treatment of AML except hydroxyurea and up to 2 days of ≤100 mg/m2/d cytarabine
Previous therapy with 5-azacytidine (i.e. for an antecedent myelodysplastic syndrome)
Patients with investigational drug therapy outside of this trial during or within 4 weeks of study entry should be discussed with the study office whether study participation is possible
Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	RWTH Aachen, Medizinische Klinik IV	Aachen	Germany	52074
2	Sozialstiftung Bamberg, Klinikum am Bruderwald, Med. Klinik V	Bamberg	Germany	96049
3	Klinikum Bayreuth, Medizinische Klinik IV	Bayreuth	Germany	95445
4	Charite Campus Benjamin Franklin, Universitätsmedizin Berlin, Medizinische Klinik III	Berlin	Germany
5	Städt. Kliniken Bielefeld gem. GmbH, Klinikum Mitte, Klinik für Hämatologie, Onkologie, Palliativmedizin	Bielefeld	Germany	33604
6	Klinikum Chemnitz, Krankenhaus Küchenwald, Klinik für Innere Medizin III	Chemnitz	Germany
7	Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I	Dresden	Germany
8	Katholische Krankenhaus Duisburg	Duisburg	Germany	47166
9	Universitätsklinikum Erlangen, Medizinische Klinik 5	Erlangen	Germany
10	Universitätsklinikum Essen, Klinik für Hämatologie	Essen	Germany
11	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)	Germany	15236
12	Klinikum der Johann Wolfgang Goethe-Universität Frakfurt am Main	Frankfurt am Main	Germany
13	Asklepios Klinik St. Georg, Hämatologische Abteilung	Hamburg	Germany
14	St. Bernward Krankenhaus Hildesheim, Medizinische Klinik II	Hildesheim	Germany
15	Westpfalz-Klinikum GmbH, Med. Klinik I	Kaiserslautern	Germany	67655
16	Stiftungsklinikum Mittelrhein, Hämatologie/ Onkologie	Koblenz	Germany	56068
17	Johannes Gutenberg-Universität Mainz Klinikum, III. Medizinische Klinik und Poliklinik	Mainz	Germany
18	Phillips Universität Marburg, Fachbereich 20, ZIM	Marburg	Germany
19	Klinikum rechts der Isar, III. Medizinische Klinik	Muenchen	Germany
20	Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A	Münster	Germany	48149
21	Klinikum Nürnberg, Medizinische Klinik 5	Nurnberg	Germany
22	Klinikum Osnabrück, Klinik für Onkologie, Hämatologie, Immunologie	Osnabruck	Germany
23	Klinikum der Universität Regensburg, Klinik und Poliklinik für Innere Medizin I	Regensburg	Germany
24	Robert-Bosch-Krankenhaus, Zentrum für Innere Medizin	Stuttgart	Germany
25	Klinikum Mutterhaus der Borromäerinnen, Innere Medizin I	Trier	Germany	2920
26	Dr. Horst-Schmidt-Kliniken	Wiesbaden	Germany	65199
27	Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II	Wurzburg	Germany