Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT00005823 | Completed Phase 3

• 4 other identifiers: CDR0000067831LRF-AML14EU-20016ISRCTN62207270
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if stronger doses of chemotherapy given over a longer period of time are as well tolerated or as effective as less intensive chemotherapy. PURPOSE: This randomized phase III trial is studying intensive regimens of chemotherapy to see how well they work compared to nonintensive regimens of chemotherapy in treating older patients with acute myeloid leukemia or myelodysplastic syndrome.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

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); refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; adult acute monocytic leukemia (M5b); secondary myelodysplastic syndromes; adult acute minimally differentiated myeloid leukemia (M0); atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable; 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 (3)

• Survival

• Response achievement

• Response duration

Secondary Outcomes (3)

• Toxicity by WHO Toxicity Grading after each treatment course

• Quality of life EORTC QLQ-C30 at 3 days, 1 month, 3 months, and 6 months from study entry

• Resource use (use of blood products, antibiotics and days in hospital) after each treatment course

Interventions

cytarabine DRUG

daunorubicin hydrochloride DRUG

etoposide DRUG

hydroxyurea DRUG

idarubicin DRUG

mitoxantrone hydrochloride DRUG

thioguanine DRUG

tretinoin DRUG

valspodar DRUG

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Acute myeloid leukemia (de novo or secondary) OR * Myelodysplastic syndrome * More than 10% myeloblasts in the bone marrow * Refractory anemia with excess blasts * Refractory anemia with excess blasts in transformation * Chronic myelomonocytic leukemia * No acute promyelocytic leukemia (FAB type M3) * No blastic phase chronic myeloid leukemia PATIENT CHARACTERISTICS: Age: * 60 and over (younger patients allowed if intensive chemotherapy not indicated) Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * No liver function test ≥ 2 times normal (for non-intensive therapy arm) Renal: * Not specified Cardiovascular: * No myocardial infarction within past 6 months in patients receiving daunorubicin or PSC 833 Other: * No other concurrent active malignancy PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No prior cytotoxic chemotherapy for leukemia Endocrine therapy: * Not specified Radiotherapy: * Not specified Surgery: * Not specified

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

Sponsors & Collaborators

• Leukemia Research Fund: lead

Study Sites (3)

Queen Elizabeth Hospital at University of Birmingham

Birmingham, England, B15 2RR, United Kingdom

Location

University College Hospital

London, England, WC1E 6AU, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XN, United Kingdom

Location

Related Publications (7)

• Seedhouse CH, Grundy M, White P, Li Y, Fisher J, Yakunina D, Moorman AV, Hoy T, Russell N, Burnett A, Pallis M; National Cancer Research Network. Sequential influences of leukemia-specific and genetic factors on p-glycoprotein expression in blasts from 817 patients entered into the National Cancer Research Network acute myeloid leukemia 14 and 15 trials. Clin Cancer Res. 2007 Dec 1;13(23):7059-66. doi: 10.1158/1078-0432.CCR-07-1484.

  PMID: 18056183 BACKGROUND

• Burnett AK, Milligan D, Hills RK, et al.: Does all-transretinoic acid (ATRA) have a role in non-APL acute myeloid leukaemia? Results from 1666 patients in three MRC trials. [Abstract] Blood 104 (11): A-1794, 2004.

  BACKGROUND

• Burnett AK, Milligan D, Goldstone A, Prentice A, McMullin MF, Dennis M, Sellwood E, Pallis M, Russell N, Hills RK, Wheatley K; United Kingdom National Cancer Research Institute Haematological Oncology Study Group. The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial. Br J Haematol. 2009 May;145(3):318-32. doi: 10.1111/j.1365-2141.2009.07604.x. Epub 2009 Mar 8.

  PMID: 19291085 RESULT

• Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, Wheatley K. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007 Mar 15;109(6):1114-24. doi: 10.1002/cncr.22496.

  PMID: 17315155 RESULT

• Burnett AK, Milligan DW, Prentice AG, et al.: Modification or dose or treatment duration has no impact on outcome of AML in older patients: preliminary results of the UK NCRI AML14 trial. [Abstract] Blood 106 (11): A-543, 2005.

  RESULT

• Burnett AK, Milligan D, Prentice AG, et al.: Low dose Ara-C versus hydroxyurea with or without retinoid in older patients not considered fit for intensive chemotherapy: the UK NCRI AML14 trial. [Abstract] Blood 104 (11): A-872, 2004.

  RESULT

• Pallis M, Truran L, Grundy M, et al.: P-Glycoprotein overexpresion and internal tandem duplications of FLT3 are characteristic of discrete populations of elderly AML patients. [Abstract] Blood 104 (11): A-196, 2004.

  RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders; Congenital Abnormalities

Interventions

Cytarabine; Daunorubicin; Etoposide; Hydroxyurea; Idarubicin; Mitoxantrone; Thioguanine; Tretinoin; valspodar

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Anemia, Refractory; Anemia; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Urea; Amides; Anthraquinones; Anthrones; Anthracenes; Quinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Alan K. Burnett, MD, FRCP

  University Hospital of Wales

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 2, 2000
• First Posted: January 27, 2003
• Study Start: December 1, 1998
• Study Completion: December 1, 2007
• Last Updated: December 18, 2013

Record last verified: 2006-09

Locations

GB (3)