Clinical Trial: Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome

This study is currently recruiting patients.

Sponsored by: Leukemia Research Fund
Information provided by: National Cancer Institute (NCI)

Purpose

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.

Condition Treatment or Intervention Phase
Acute Myeloid Leukemia
adult acute monoblastic and acute monocytic leukemia
atypical chronic myeloid leukemia
Chronic Myelomonocytic Leukemia
myelodysplastic and myeloproliferative disease
 Drug: PSC 833
 Drug: cytarabine
 Drug: daunorubicin
 Drug: etoposide
 Drug: hydroxyurea
 Drug: idarubicin
 Drug: mitoxantrone
 Drug: thioguanine
 Drug: tretinoin
 Procedure: chemosensitization/potentiation
 Procedure: chemotherapy
 Procedure: high-dose chemotherapy
Phase III

MedlinePlus related topics:  Blood and Blood Disorders;   Cancer;   Cancer Alternative Therapy;   Immune System and Disorders;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood;   Lymphatic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Phase III Randomized Study of Intensive Versus Nonintensive Chemotherapy in Older Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Further Study Details: 

OBJECTIVES:

  • 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.

OUTLINE: This is a randomized study. Patients are randomized or electively assigned to either intensive or nonintensive chemotherapy.

Intensive chemotherapy

  • 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.
  • 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.

Non-intensive chemotherapy

  • 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. Quality of life is assessed at study entry, and then at 1, 3, and 6 months.

Patients are followed at one year.

PROJECTED ACCRUAL: Approximately 2,000 patients (1,200 to intensive arm and 800 to nonintensive arm) will be accrued for this study over 5 years.

Eligibility

Ages Eligible for Study:  60 Years and above,  Genders Eligible for Study:  Both

Criteria

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 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:

  • Not specified

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:

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Location and Contact Information


United Kingdom, England
      Queen Elizabeth Hospital at University of Birmingham, Birmingham,  England,  B15 2RR,  United Kingdom; Recruiting
Keith Wheatley, PhD  44-121-472-1311    k.wheatley@bham.ac.uk 

      University College Hospital, London,  England,  WC1E 6AU,  United Kingdom; Recruiting
Antony H. Goldstone, FRCP  44-20-7380-9678    anthony.golstone@uclh.org 

United Kingdom, Wales
      University Hospital of Wales, Cardiff,  Wales,  CF14 4XN,  United Kingdom; Recruiting
Alan K. Burnett, MD, FRCP  44-29-2074-2375    burnettak@cardiff.ac.uk 

Study chairs or principal investigators

Alan K. Burnett, MD, FRCP,  Study Chair,  University Hospital of Wales   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000067831; LRF-AML14; EU-20016; NCT00005823
Record last reviewed:  September 2003
Last Updated:  April 4, 2005
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005823
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005