Please select the eligibility criteria that correspond to the clinical trial below.
Title: AML2003 - Randomized Comparison Between Standard-Therapy and Intensified Therapy for Adult Acute Myeloid Leukemia Patients <= 60 Years. A Prospective, Randomized, Multi-center Therapy-Optimizing-Study.
Brief Summary: AML2003 is a prospective randomized trial, to investigate the value of early allogeneic stem cell transplantation in aplasia after induction therapy for high risk patients with acute myeloid leukemia.


Options:
A: 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.

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.
B: Inclusion Criteria:

* de novo or secondary acute myeloid leukemia FAB-subtypes M0-M2 and M4-M7
* de novo or secondary myelodysplastic syndrome WHO-type RAEB-2
* age 16 to 60 years
* written informed consent

Exclusion Criteria:

* severe comorbidities
* severe, uncontrolled complications of the leukemia
* prior therapy for AML/MDS
* other simultaneous hematological malignancies
* HIV-Infection
* known allergies against study medication
* pregnancy
* missing written informed consent
C: Inclusion Criteria:

* Morphologically confirmed acute myeloid leukemia (AML) (greater than 20% blasts in the peripheral blood or marrow) meeting any of the following criteria:

  * Recurrent cytogenetic translocations

    * t(8;21)(q22;q22)
    * Bone marrow eosinophil abnormalities

      * inv(16)(p13;q22)
      * t(16;16)(p13;q22)
    * 11q23 abnormalities
  * Multilineage dysplasia without presence of myelodysplastic syndromes (MDS)
  * Minimally differentiated AML
  * AML without maturation
  * AML with maturation
  * AML not otherwise categorized
  * Acute myelomonocytic leukemia
  * Acute monocytic leukemia
  * Acute erythroid leukemia
  * Acute megakaryocytic leukemia
  * Acute basophilic leukemia
* Patients undergoing allogeneic transplantation must have a sibling donor match defined as human leukocyte antigen (HLA) match or haplotype match with one locus mismatch on other haplotype
* Age 16 to 60
* Eastern Cooperative Oncology Group (ECOG) performance status 0-4
* Aspartate aminotransferase (AST) less than 4 times upper limit of normal (ULN)
* Alkaline phosphatase less than 4 times ULN
* Creatinine no greater than 2.0 mg/dL
* Creatinine clearance at least 50 mL/min
* Left ventricular ejection fraction (LVEF) at least 45% by post-induction multigated acquisition (MUGA) scan
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* Prior hydroxyurea allowed
* Prior corticosteroids allowed

Exclusion Criteria:

* Recurrent cytogenetic translocations

  * Acute promyelocytic leukemia (PML) with t(15;17)(q22;q21)
  * Variant acute PML with t(v;17)
* Multilineage dysplasia with prior MDS
* Acute panmyelosis with myelofibrosis

  * Blastic transformation of chronic myelogenous leukemia
  * Secondary AML (chemotherapy-induced or evolved from MDS)
  * Pregnant or nursing
  * Bilirubin greater than 2.0 mg/dL (unless related to Gilbert's syndrome or hemolysis)
  * Significant cardiac disease requiring active therapy (e.g., digoxin, diuretics, antiarrhythmics, or antianginal medications)
  * Prior biologic therapy
  * Prior cytotoxic chemotherapy for any malignancy
  * Prior radiotherapy for any malignancy
D: Inclusion Criteria:

* Newly diagnosed AML defined according to the World Health Organization (WHO)-classification (excluding acute promyelocytic leukemia \[APL\])
* Ages 18-60 years
* Written informed consent of each patient at study entry.
* Molecular and cytogenetical diagnostics on initial bone marrow and peripheral blood specimen at the central reference laboratories

Exclusion Criteria:

* Bleeding independent of the AML
* Acute promyelocytic leukemia
* Uncontrollable infection
* Participation in a concurrent clinical study
* Insufficiency of the kidneys (creatinine \> 1.5x upper normal serum level), of the liver (bilirubin, AST or AP \> 2x upper normal serum level), severe obstructive or restrictive ventilation disorder, heart failure New York Heart Association (NYHA) III/IV
* Severe neurological or psychiatric disorder interfering with ability to give an informed consent.
* No consent for registration, storage and processing of the individual disease-characteristics and course.
* Performance status WHO \> 2
* Pregnancy

Answer: B