Prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients > 60 years with acute myeloid leukemia who are ineligible for induction chemotherapy

Phase 2

• Conditions: C92.9; Myeloid leukaemia, unspecified

• Registration Number: DRKS00000733
• Lead Sponsor: niversitätsklinikum Freiburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04-19
• Study Completion: 2016-02-23
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 204

Inclusion Criteria

1.Written informed consent obtained according to international guidelines and local law;
2.Male or female patients aged > 60 years without upper age limit;
3.Patients with primary or secondary AML according to WHO (= 20% BM blasts) who are not expected to benefit from standard remission-induction chemotherapy;
4.Patients with < 30 000 leukocytes/µl;
5.Performance status ECOG 0, 1, 2;
6.Age-adjusted normal cardiac and kidney function (creatinine < 2.0 mg/dl unless leukemia-related);
7.Ability to understand the nature of the study and the study related procedures and to comply with them.

Exclusion Criteria

1.AML of FAB subtype M3;
2.Previous remission-induction chemotherapy for MDS or AML, previous auto-/allografting;
3.Previous treatment with DAC, 5-azacytidine, VPA or another HDAC inhibitor, or ATRA;
4.Low-dose chemotherapy (e.g. hydroxyurea, cytosine arabinoside, melphalan, clofarabine etc.) within 8 weeks prior to DAC treatment, except for cytoreduction of leukocytosis = 30 000/µl with hydroxyurea, as proscribed by the study protocol (section 7.3 and 7.4);
5.Treatment with tyrosine kinase Inhibitors, immunomodulating agents (IMIDS) and other investigational AML treatments within previous 8 weeks;
6.Treatment with cytokines within previous 4 weeks;
7.Concomitant therapy which is considered relevant for the evaluation of efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy);
8.Other malignancy requiring treatment (previous chemotherapy for other malignancies is not an exclusion criteria);
9.Cardiac insufficiency NYHA IV;
10.Insufficient hepatic function (bilirubin, AST or ALT > = 2.5 x Upper Limit of Normal (ULN));
11.Fatal hepatic function disorder during treatment with valproic acid in siblings;
12.Hepatic porphyria;
13.Manifest serious pancreatic function disorder;
14.Plasmatic coagulation disorder not related to AML;
15.Hepatitis B or C;
16.HIV infection;
17.Other uncontrolled active infections;
18.Known allergy against soy beans or peanuts;
19.Psychiatric disorder that interferes with treatment;
20.Patient without legal capacity who is unable to understand the nature, significance and consequences of the study;
21.Known hypersensitivity to, or intolerance of, one of the trial drugs, another retinoid or the excipients of the trial drugs;
22.Concomitant use of any other investigational drug or participation in a clinical trial within the last thirty days before the start of this study;
23.Female patients who are pregnant or breast feeding;
24.Fertile patients refusing to use safe contraceptive methods during the study (for details see clinical trial protocol section 5.3);
25.Known or persistent abuse of medication, drugs or alcohol.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective best response rate (complete remission (CR) and partial remission (PR)) (at the end of the study)

Secondary Outcome Measures

Name	Time	Method
Overall best response rate (CR, PR and antileukemic effect (ALE)), progression-free survival (PFS), overall survival (OS), quality of life (QOL), number of nights in hospital, safety (at the end of the study)