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Phase III Randomized Trial of Induction with DAT (DNR/ARA-C/TG) vs ADE (ARA-C/DNR/VP-16) vs MAC (DHAD/ARA-C) and of Short DAT Consolidation vs Extended Consolidation with Alternating COAP (CTX/VCR/ARA-C/PRED) and DAT and of IFN-A Maintenance vs No Maintenance in Older Patients with AML

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Alternate Title

Combination Chemotherapy With or Without Interferon Alfa in Treating Older Patients With Acute Myeloid Leukemia

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosedover 55MRC-LEUK-AML11
EU-91023

Objectives

I.  Determine the remission rate, duration of remission, survival, and 
toxicity and supportive care requirement of patients with de novo or secondary 
acute myeloid leukemia randomized for remission induction to DAT 
(daunorubicin/cytarabine/thioguanine) vs. ADE 
(cytarabine/daunorubicin/etoposide) vs. MAC (mitoxantrone/cytarabine).

II.  Determine the duration of remission and survival of patients randomized 
for consolidation to a short course of DAT vs. a long course of alternating 
DAT and COAP (cyclophosphamide/vincristine/cytarabine/prednisone).

III.  Assess the duration of remission and survival of patients randomized for 
maintenance to interferon alpha vs. no maintenance therapy.

IV.  Determine the efficacy of immunophenotypic, morphologic, cytogenetic, and 
molecular genetic studies of blood and bone marrow for detecting minimum 
residual disease.

Entry Criteria

Disease Characteristics:


De novo or secondary acute myeloid leukemia in patients not
eligible for autologous bone marrow therapy (ABMT)
  Patients eligible for ABMT enter protocol MRC-LEUK-AML10

  At least 30% blast cells in marrow if leukemia is secondary
  to a pre-existing hematologic disorder

No chronic myeloid leukemia in blast crisis


Prior/Concurrent Therapy:


Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy for leukemia

Endocrine therapy:
  Not specified

Radiotherapy:
  Not specified

Surgery:
  Not applicable


Patient Characteristics:


Age:
  Over age 55 or ineligible for ABMT

Performance status:
  1-4

Hematopoietic:
  See Disease Characteristics

Hepatic:
  Not specified

Renal:
  Not specified

Other:
  Fit for intensive chemotherapy
  No concurrent active malignancy


Expected Enrollment

1,500 patients will be randomized for Induction over 3-4 years.  Approximately 
200 patients annually will be eligible for randomization for Consolidation and 
Maintenance.

Outline

Randomized study.  Patients are randomized 1:1:2 for remission induction on 
Arms I, II, and III, after which all patients who achieve CR receive 1 course 
of consolidation therapy (Consolidation I).  Patients who remain in remission 
are then randomized for further consolidation on Arms IV and V and for 
maintenance therapy vs. observation on Arms VI and VII.

INDUCTION.

Induction Arm I:  3-Drug Combination Chemotherapy.  DAT:  Daunorubicin, DNR, 
NSC-82151; Cytarabine, ARA-C, NSC-63878; Thioguanine, TG, NSC-752.

Induction Arm II:  3-Drug Combination Chemotherapy.  ADE:  ARA-C; DNR; 
Etoposide, VP-16, NSC-141540.

Induction Arm III:  2-Drug Combination Chemotherapy.  MAC:  Mitoxantrone, 
DHAD, NSC-301739; ARA-C.

CONSOLIDATION.

Consolidation I:  3-Drug Combination Chemotherapy.  DAT.

Arm IV - Consolidation II:  4-Drug Combination Chemotherapy alternating with 
3-Drug Combination Chemotherapy.  COAP:  Cyclophosphamide, CTX, NSC-26271; 
Vincristine, VCR, NSC-67574; ARA-C; Prednisolone, PRDL, NSC-9900; followed by 
DAT; followed by COAP.

Arm V:  No further consolidation therapy.  Observation.

MAINTENANCE.

Arm VI:  Biological Response Modifier Therapy.  Interferon alpha (Hoffmann-La 
Roche), IFN-A, NSC-367982.

Arm VII:  No further treatment.

Published Results

Goldstone AH, Burnett AK, Wheatley K, et al.: Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood 98 (5): 1302-11, 2001.[PUBMED Abstract]

Grimwade D, Walker H, Harrison G, et al.: The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98 (5): 1312-20, 2001.[PUBMED Abstract]

Goldstone AH, Burnett AK, Wheatley K, et al.: Superior CR rates with DAT induction compared to ADE or MAC in older patients with AML, but three additional courses of consolidation chemotherapy and mainenance with interferon do not improve survival: results of the MRC, AML 11 trial. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A19, 1999.

Related Publications

Wheatley K, Goldstone AH, Littlewood T, et al.: Randomized placebo-controlled trial of granulocyte colony stimulating factor (G-CSF) as supportive care after induction chemotherapy in adult patients with acute myeloid leukaemia: a study of the United Kingdom Medical Research Council Adult Leukaemia Working Party. Br J Haematol 146 (1): 54-63, 2009.[PUBMED Abstract]

Peniket A, Wainscoat J, Side L, et al.: Del (9q) AML: clinical and cytological characteristics and prognostic implications. Br J Haematol 129 (2): 210-20, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Medical Research Council's Working Party on Leukemia in Adults and Children

Alan Burnett, MD, FRCP, Protocol chair
Ph: 44-29-2074-2375
Email: burnettak@cardiff.ac.uk

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.

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