|Phase III Randomized Study of Intensive Versus Nonintensive Chemotherapy in Older Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.
First Published: 6/1/2000  Last Modified: 7/15/2009
Basic Trial Information
Trial Contact Information
Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.
Basic Trial Information
|Phase III||Treatment||Closed||60 and over||LRF-AML14|
EU-20016, NCT00005823, ISRCTN62207270
- Compare the response rate, survival, quality of life, and supportive care requirements with intensive versus nonintensive chemotherapy in older patients with acute myeloid leukemia or high risk myelodysplastic syndrome.
- Compare response achievement, response duration, survival, toxicity and supportive care requirements with differing doses of daunorubicin and cytarabine in these patients receiving intensive chemotherapy.
- Determine the efficacy of PSC 833 in enhancing the effects of daunorubicin in these patients receiving intensive chemotherapy.
- Compare relapse rate, deaths in complete remission, disease free survival, and survival with short versus long intensive chemotherapy in these patients.
- Compare response achievement, response duration, survival, toxicity, quality of life, and resource use with hydroxyurea versus cytarabine in these patients receiving low dose chemotherapy.
- Determine response achievement, response duration, survival, toxicity, quality of life, and supportive care requirements with the addition of tretinoin to the nonintensive chemotherapy in these patients.
- Assess the correlation between P-gp and BCL-2 in family members and treatment outcomes and other prognostic factors in these patients with these treatment regimens.
- Acute myeloid leukemia (de novo or secondary)
- 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
- No prior cytotoxic chemotherapy for leukemia
- 60 and over (younger patients allowed if intensive
chemotherapy not indicated)
- No liver function test ≥ 2 times normal (for non-intensive therapy arm)
- No myocardial infarction within past 6 months in patients
receiving daunorubicin or PSC 833
- No other concurrent active malignancy
Approximately 2,000 patients (1,200 to intensive arm and 800 to nonintensive
arm) will be accrued for this study over 5 years.
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
This is a randomized, multicenter study. Patients are randomized or electively assigned to either
intensive or nonintensive chemotherapy*.
- Induction therapy: Patients are randomized to 1 of 6 treatment arms. Patients receive 2 courses of chemotherapy comprising 1 of 2 daunorubicin doses, 1 of 2 cytarabine doses, thioguanine, and with or without PSC 833.
Patients receive daunorubicin IV once daily on days 1-3 with cytarabine IV twice daily and oral thioguanine once daily on days 1-10 during course 1. Treatment repeats in approximately 31 days as in course 1 except cytarabine and thioguanine are given only on days 1-8.
- Arm I: Patients receive higher dose of daunorubicin, lower dose of cytarabine, and thioguanine.
- Arm II: Patients receive higher dose of daunorubicin, higher dose of cytarabine, and thioguanine.
- Arm III: Patients receive lower dose of daunorubicin, lower dose of cytarabine, and thioguanine.
- Arm IV: Patients receive lower dose of daunorubicin, higher dose of cytarabine, and thioguanine.
- Arm V: Patients receive treatment as in arm III in combination with continuous infusion of PSC 833 beginning day 1.
- Arm VI: Patients receive treatment as in arm IV in combination with continuous infusion of PSC 833 beginning on day 1.
Patients with refractory disease after the first course of induction
chemotherapy may continue with the intensive protocol arm or enter the
nonintensive arm*. Patients who do not achieve complete remission after completion of induction chemotherapy are removed from study. Patients in complete remission after induction therapy receive consolidation therapy.
- Consolidation therapy: Patients in complete remission after induction are randomized to either short or long consolidation.
- Short consolidation: Patients receive mitoxantrone IV on days 1-3 and cytarabine IV over 2 hours twice daily on days 1-3.
- Long consolidation: Patients complete short consolidation and then receive idarubicin IV over 5 minutes once daily on days 1 and 3, cytarabine IV over 2 hours twice daily and etoposide IV over 1 hour once daily on days 1-3.
- Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive oral hydroxyurea as necessary to control WBC count until treatment failure.
- Arm II: Patients receive hydroxyurea as in arm I and oral tretinoin daily for up to 16 weeks.
- Arm III: Patients receive low dose cytarabine subcutaneously twice daily on days 1-10 every 28 days for a minimum of 4 courses.
- Arm IV: Patients receive cytarabine as in arm III plus oral tretinoin daily for up to 16 weeks.
[Note: *Patients with liver function test > 2 times upper limit of normal are not eligible for nonintensive randomization]
Quality of life is assessed at study entry, and then at 1, 3, and 6
Patients are followed at one year.Published Results
Burnett AK, Milligan D, Goldstone A, et al.: 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 145 (3): 318-32, 2009.[PUBMED Abstract]
Burnett AK, Milligan D, Prentice AG, et al.: 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 109 (6): 1114-24, 2007.[PUBMED Abstract]
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.
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.
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.Related Publications
Seedhouse CH, Grundy M, White P, et al.: 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 13 (23): 7059-66, 2007.[PUBMED Abstract]
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.
Trial Contact Information
Trial Lead Organizations
Leukemia Research Fund
|Alan Burnett, MD, FRCP, Protocol chair|
|Official Title|| ||A Randomized Trial for Patients with Acute Myeloid Leukemia or High Risk Myelodysplatic Syndrome Aged 60 or Over|
|Trial Start Date|| ||1998-12-01|
|Registered in ClinicalTrials.gov|| ||NCT00005823|
|Date Submitted to PDQ|| ||2000-03-23|
|Information Last Verified|| ||2006-09-17|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.