Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation
Brief Summary: RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the transplanted stem cells. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. If the patient's stem cells are to be transplanted, the patient is also treated with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab ozogamicin, and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia.


Options:
A: 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
B: 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
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:

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.

Answer: C