Combination Chemotherapy, Interleukin-2, and Peripheral Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

RATIONALE: Giving combination chemotherapy before a peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood or bone marrow and stored. More chemotherapy or radiation therapy is given prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. Interleukin-2 may stimulate the patient's white blood cells to kill cancer cells. PURPOSE: This randomized phase III trial is studying two different regimens of combination chemotherapy, interleukin-2, and peripheral stem cell transplant and comparing them to see how well they work in treating patients with acute myeloid leukemia.

Sex

All

Minimum age

15 Years

Maximum age

60 Years

DISEASE CHARACTERISTICS:

* First randomization:

  * Untreated newly diagnosed acute myeloid leukemia (AML)
  * At least 30% blasts in bone marrow
  * All cytological types of AML except acute promyelocytic leukemia (M3)
  * No blast crisis of chronic myelogenous leukemia
  * No leukemias supervening after other myeloproliferative disease
  * No leukemias supervening after overt myelodysplastic disorders (e.g., refractory anemia with excess blasts) for more than 6 months duration
* Second randomization:

  * Must have achieved complete remission with full hematologic recovery following consolidation treatment
  * No HLA identical family donor
  * Not eligible for allograft
  * No high risk patient (under age 40) for whom an unrelated bone marrow donor has been found within 8 weeks of beginning consolidation treatment

PATIENT CHARACTERISTICS:

Age:

* 15 to 60

Performance status:

* WHO 0-3 (first randomization)
* WHO 0-2 (second randomization)

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin no greater than 3 times upper limit of normal (ULN)

Renal:

* Creatinine no greater than 3 times ULN

Cardiovascular:

* No severe heart failure requiring diuretics
* Ejection fraction at least 50%

Other:

* First randomization:

  * No other progressive malignant disease except the following:

    * Secondary acute leukemias following curatively treated Hodgkin's disease (even if treated with anthracyclines)
    * Other curatively treated malignancies
    * Secondary leukemias following other exposure to alkylating agents or radiotherapy for other reason
  * No uncontrolled infection
  * No severe concurrent neurologic or psychiatric disease
  * No psychological, familial, sociological, or geographical condition that could preclude compliance
* Second randomization:

  * No nonmalignant systemic illness that would increase risk of participation in study
  * No uncontrolled infection
  * No other progressive malignant disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy for AML except hydroxyurea
* Less than 7 days of prior hydroxyurea

Endocrine therapy:

* No more than 7 days of prior corticosteroid therapy for AML

Radiotherapy:

* No prior radiotherapy for AML

Surgery:

* Not specified

• BACKGROUNDMaurillo L, Buccisano F, Spagnoli A, et al.: In acute myeloid leukemia, the use in induction of standard dose arac is associated with a better quality of response as compared to an induction regimen containing high dose arac. [Abstract] Blood 114 (22): A-1584, 2009.
• RESULTAslanyan MG, Langemeijer SMC, Cilloni D, et al.: Incidence and clinical impact of TET2 mutations in acute myeloid leukemia patients treated within the EORTC/GIMEMA AML-12/06991 AML trial. [Abstract] Blood 114 (22): A-2609, 2009.
• RESULTWillemze R, Suciu S, Mandelli F, et al.: Value of low dose IL-2 as maintenance following consolidation treatment or autologous transplantation in acute myelogenous leukemia (AML) patients aged 15-60 years who reached CR after high dose (HD-AraC) vs standard dose (SD-AraC) cytosine arabinoside during induction: results of the AML-12 trial of EORTC and GIMEMA Leukemia Groups. [Abstract] Blood 114 (22): A-791, 2009.
• DERIVEDBaron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, Halkes CJM, Thomas X, Vrhovac R, Albano F, Lefrere F Sr, Sica S, Mancini M, Venditti A, Hagemeijer A, Jansen JH, Amadori S, de Witte T, Willemze R, Suciu S. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype. Haematologica. 2019 Jun;104(6):1168-1175. doi: 10.3324/haematol.2018.204826. Epub 2018 Dec 6. PMID 30523055
• DERIVEDBaron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, Halkes CJM, Thomas X, Vrhovac R, Specchia G, Lefrere F Sr, Sica S, Mancini M, Venditti A, Hagemeijer A, Becker H, Jansen JH, Amadori S, de Witte T, Willemze R, Suciu S. Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15-60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials. Ann Hematol. 2018 Oct;97(10):1785-1795. doi: 10.1007/s00277-018-3396-4. Epub 2018 Jun 20. PMID 29926156
• DERIVEDKroeze LI, Aslanyan MG, van Rooij A, Koorenhof-Scheele TN, Massop M, Carell T, Boezeman JB, Marie JP, Halkes CJ, de Witte T, Huls G, Suciu S, Wevers RA, van der Reijden BA, Jansen JH; EORTC Leukemia Group and GIMEMA. Characterization of acute myeloid leukemia based on levels of global hydroxymethylation. Blood. 2014 Aug 14;124(7):1110-8. doi: 10.1182/blood-2013-08-518514. Epub 2014 Jul 1.