Clinical trial of low-dose decitabine (DAC) administered alone or in combination with the valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients > 60 years with acute myeloid leukemia who are ineligible for standard chemotherapy

Phase 1

• Conditions: Patients older than 60 years with acute myeloid leukemia according to WHO (= 20 % blasts in the peripheral blood (pB) or bone marrow (BM)) not qualifying for, or not consenting to, standard remission-induction chemotherapy or immediate allografting; MedDRA version: 17.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-009916-33-DE
• Lead Sponsor: niversity Medical Center Freiburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-10-11
• Study Completion: 2016-02-23
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

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% blasts in the peripheral blood (pB) or bone marrow (BM)) 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.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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion Criteria

1.AML of FAB subtype M3;
2.Previous remission-induction chemotherapy for MDS or AML, previous allografting;
3.Previous treatment with DAC, 5-azacytidine, VPA or another HDAC inhibitor, or ATRA;
4.Low-dose chemotherapy (e.g. hydroxyurea, cytosine arabinoside (Ara-C), melphalan, clofarabine etc.) within 4 weeks prior to DAC treatment, except for cytoreduction of leukocytosis = 30 000/µl with hydroxyurea or Ara-C as proscribed by the study protocol (section 7.3 and 7.4); the patient must have recovered from all clinically relevant reversible non-hematologic toxicities;
5.Treatment with tyrosine kinase inhibitors, immunomodulating agents (IMIDS) or other investigational AML treatment within the last 4 weeks or in a time period of drug half-life x 5 (whatever is shorter) before the first administration of DAC;
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)) (unless leukemia-related);
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.Known active hepatitis B or C;
16.Known 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; simultaneous participation in registry and diagnostic trials is allowed;
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 clinical trial of medicinal product
• Study Design: Not specified