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

NCT00004128 | Unknown Phase 3

• 3 other identifiers: CDR0000067356EORTC-06991GIMEMA-EORTC-06991
• Study Type: interventional
• Target: 2,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Leukemia

Keywords

untreated adult acute myeloid leukemia; adult acute erythroid leukemia (M6); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute megakaryoblastic leukemia (M7); adult acute monocytic leukemia (M5b); adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22)

Outcome Measures

Primary Outcomes (2)

• Duration of overall survival and disease-free survival after first randomization

• Duration of overall survival and disease-free survival after second randomization

Secondary Outcomes (7)

• Response after induction and consolidation

• Toxicity measured by Cancer and Leukemia Group B (CALGB) CTCAE v3.0 after induction and consolidation

• Disease-free survival after complete remission (CR)

• Disease-free interval from CR

• Time to death in CR

Interventions

aldesleukin BIOLOGICAL

filgrastim BIOLOGICAL

busulfan DRUG

cyclophosphamide DRUG

cytarabine DRUG

daunorubicin hydrochloride DRUG

etoposide DRUG

autologous bone marrow transplantation PROCEDURE

peripheral blood stem cell transplantation PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Gruppo Italiano Malattie EMatologiche dell'Adulto: collaborator

Related Publications (7)

• Maurillo 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.

  BACKGROUND

• Aslanyan 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.

  RESULT

• Willemze 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.

  RESULT

• Baron 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 DERIVED

• Baron 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 DERIVED

• Kroeze 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.

  PMID: 24986689 DERIVED

• Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrere F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. doi: 10.1200/JCO.2013.51.8571. Epub 2013 Dec 2.

  PMID: 24297940 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Congenital Abnormalities

Interventions

aldesleukin; Filgrastim; Busulfan; Cyclophosphamide; Cytarabine; Daunorubicin; Etoposide; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Roel Willemze, MD, PhD

  Leiden University Medical Center

• Giovanna Meloni, MD

  University La Sapienza

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: December 10, 1999
• First Posted: January 27, 2003
• Study Start: September 1, 1999
• Primary Completion: January 1, 2008
• Last Updated: December 23, 2009

Record last verified: 2008-04