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Clinical Trials (PDQ®)

NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Comparison of Allogeneic Bone Marrow Transplant vs Autologous Bone Marrow Transplant vs High-Dose ARA-C Consolidation Following Remission Induction with ARA-C/Idarubicin in Adult ANLL

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosed16 to 55NCIE-3489
CLB-9120, SWOG-9034, EST-3489, E3489

Objectives

I.  Compare the duration of CR and survival of previously untreated adults 
with ANLL who, following remission induction with cytosine 
arabinoside/idarubicin, are randomized to autologous bone marrow therapy with 
marrow purged with 4-hydroperoxycyclophosphamide vs. conventional 
consolidation chemotherapy with one course of high-dose cytosine arabinoside.

II.  Assess any differences in outcome for patients receiving allogeneic bone 
marrow transplant as post-remission therapy vs. autologous bone marrow therapy 
or consolidation chemotherapy.

III.  Examine the influence of age, cell surface markers, and karyotype 
abnormalities on outcome in the three post-remission therapy groups.

Entry Criteria

Disease Characteristics:


Acute myeloid leukemia FAB types 1-7, i.e.,

  Myeloblastic with or without maturation
  Promyelocytic
  Myelomonocytic
  Monocytic
  Erythroleukemia
  Megakaryocytic

Minimally differentiated AML (FAB type M0) eligible provided
all the following criteria are met:
  Blast cells (30% or more) identified without typical
  features of myeloblasts

  Negative myeloperoxidase by standard cytochemical methods
  (i.e., less than 3% positive)

  Positive myeloid antigens (CD13 or CD33, or more rarely
  CD11b, CD11c, CD14, or CD15)

  Negative lymphoid-specific antigens (CD10, CD19, CD22, CD2,
  CD3) except TdT, CD4, and CD7

Blastic transformation of CML excluded

Morphologic proof of disease required (bone marrow aspirate
smears or touch preps of marrow biopsies)

Karyotype submissions and submission of samples for surface
markers required

ECOG patients must be concurrently registered on ancillary
study EST-1485

SWOG patients must be concurrently registered on ancillary
study SWOG-8750 or SWOG-9007

CALGB patients must be concurrently registered on ancillary
studies CLB-8361 and CLB-8364


Prior/Concurrent Therapy:


Biologic therapy:
  Not specified

Chemotherapy:
  No prior cytotoxic chemotherapy
  Prior hydroxyurea allowed

Endocrine therapy:
  Prior corticosteroids allowed

Radiotherapy:
  No prior radiotherapy

Surgery:
  Not applicable


Patient Characteristics:


Age:
  16 to 55

Performance status:
  Not specified

Hematopoietic:
  Not specified

Hepatic:
  Bilirubin no greater than 2.0 mg/dl

Renal:
  Creatinine less than 2.0 mg/dl
  Creatinine clearance (calculated) at least 70 ml/min

Cardiovascular:
  Ejection fraction in normal range
  No significant cardiac disease requiring therapy with
     agents such as digoxin, diuretics, antiarrhythmics, or 
     antianginal medicines

Eligibility requirements for post-remission therapy (including
allogeneic bone marrow transplant):

  Must have achieved documented CR
  Must be free of infection off all antibiotics
  Must have histocompatible sibling under age 65
  ECOG performance status 0 or 1
  Bilirubin less than 2.0 mg/dl
  Alkaline phosphatase less than 4 x normal
  SGOT less than 4 x normal
  Creatinine less than 2.0 mg/dl
  Creatinine clearance at least 70 ml/min
  Cardiac ejection fraction normal
  No intercurrent organ damage
  No medical problem that might jeopardize therapeutic
     outcome


Expected Enrollment

808 patients will be registered on the Induction regimen over 4-5 years.  It 
is anticipated that of these, approximately 133 will be eligible for 
allogeneic bone marrow transplantation.

Outline

All patients receive remission induction therapy on Regimen A.  All patients 
in CR receive an additional (modified) course of remission induction 
chemotherapy.  Patients who have a histocompatible sibling not over the age of 
65 years are then assigned to post-remission allogeneic bone marrow transplant 
on Regimen B, while all others are randomized for post-remission therapy on 
Arms I and II.

Induction.

Regimen A:  2-Drug Combination Chemotherapy.  Idarubicin, IDA, NSC-256439; 
Cytarabine, ARA-C, NSC-63878.

Post-Remission Therapy.

Regimen B:  Marrow Ablation with 2-Drug Combination Chemotherapy followed by 
Allogeneic Bone Marrow Transplantation and GVHD Prophylaxis.  Busulfan, BU, 
NSC-750; Cyclophosphamide, CTX, NSC-26271; followed by infusion of allogeneic 
marrow.  GVHD prophylaxis according to institutional procedures is mandatory 
(T-cell depletion techniques are not acceptable).

Arm I:  Marrow Ablation with 2-Drug Combination Chemotherapy Followed by 
Autologous Bone Marrow Transplantation.  BU; CTX; followed by infusion of 
4-Hydroperoxycyclophosphamide (4-HC)-treated autologous bone marrow.

Arm II:  Single-Agent Chemotherapy.  High-dose ARA-C.

Published Results

Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96 (13): 4075-83, 2000.[PUBMED Abstract]

Cassileth PA, Harrington DP, Appelbaum FR, et al.: Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 339 (23): 1649-56, 1998.[PUBMED Abstract]

Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of pre- and post- remission therapy in adult acute myeloid leukemia (AML): a SWOG/ECOG intergroup study. [Abstract] Blood 92 (10 suppl 1): A-2795, 678a, 1998.

Cassileth P, Harrington D, Paietta E, et al.: Comparison of autologous bone marrow transplant (AUTOBMT) with high-dose cytarabine (HDAC) in adult acute myeloid leukemia (AML) in first remission (CR1). [Abstract] Proceedings of the American Society of Clinical Oncology 16: A311, 1997.

Cassileth PA, Andersen JW, Bennett JM, et al.: Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group. Leukemia 6 (Suppl 2): 116-9, 1992.[PUBMED Abstract]

Related Publications

Wiernik PH, Sun Z, Gundacker H, et al.: Prognostic implications of additional chromosome abnormalities among patients with de novo acute promyelocytic leukemia with t(15;17). Med Oncol 29 (3): 2095-101, 2012.[PUBMED Abstract]

Rowe JM, Kim HT, Cassileth PA, et al.: Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis: a report on 1980 patients registered to 6 studies conducted by the Eastern Cooperative Oncology Group. Cancer 116 (21): 5012-21, 2010.[PUBMED Abstract]

Rowe JM, Sun Z, Cassileth PA, et al.: Treatment-related mortality and relapse rate from time of initiation of post-remission therapy for patients receiving allogeneic transplantation, autologous transplantation or intensive chemotherapy: a report from the Eastern Cooperative Oncology Group (ECOG). [Abstract] Blood 112 (11): A-49, 2008.

Appelbaum FR, Gundacker H, Head DR, et al.: Age and acute myeloid leukemia. Blood 107 (9): 3481-5, 2006.[PUBMED Abstract]

Wilson CS, Davidson GS, Martin SB, et al.: Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood 108 (2): 685-96, 2006.[PUBMED Abstract]

Paietta E, Goloubeva O, Neuberg D, et al.: A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes. Cytometry B Clin Cytom 59B (1): 1-9, 2004.[PUBMED Abstract]

Rowe JM, Kim HT, Cassileth PA, et al.: Time to complete remission is not a significant prognostic factor in AML: a report on 1,959 consecutive patients registered to 6 studies of the Eastern Cooperative Oncology Group (ECOG). [Abstract] Blood 104 (11): A-862, 2004.

Tallman MS, Kim HT, Paietta E, et al.: Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid leukemia: a report from the Eastern Cooperative Oncology Group. J Clin Oncol 22 (7): 1276-86, 2004.[PUBMED Abstract]

Hulshizer C, Paietta E, Bennett JM, et al.: Comparison of cytogenetics in patients with Acute Myeloid Leukemia (AML): French-American-British (FAB) classification M5 versus non-M5. [Abstract] Blood 100 (11 pt 2): A-4497, 2002.

Paietta E, Goloubeva O, Bennett JM, et al.: A surrogate marker profile for acute promyelocytic leukemia (APL) and the association of immunophenotypic markers with morphologic and molecular subtypes of APL. [Abstract] Blood 100 (11 pt 2): A-4434, 2002.

Tallman MS, Neuberg D, Bennett JM, et al.: Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience. Blood 96 (7): 2405-11, 2000.[PUBMED Abstract]

Tallman MS, Neuberg D, Bennett JM, et al.: Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group (ECOG) experience. [Abstract] Blood 94 (10 suppl 1, pt 1): A-2656, 596a, 1999.

Paietta E, Andersen J, Yunis J, et al.: Acute myeloid leukaemia expressing the leucocyte integrin CD11b-a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis. Eastern Cooperative Oncology Group. Br J Haematol 100 (2): 265-72, 1998.[PUBMED Abstract]

Paietta E, Racevskis J, Bennett JM, et al.: Biologic heterogeneity in Philadelphia chromosome-positive acute leukemia with myeloid morphology: the Eastern Cooperative Oncology Group experience. Leukemia 12 (12): 1881-5, 1998.[PUBMED Abstract]

Wiernik P, Lee S, Cassileth PA, et al.: Non-caucasians with acute myeloid leukemia (AML) have a higher frequency of FAB M3 type than caucasians. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A158, 41a, 1998.

Banker DE, Groudine M, Norwood T, et al.: Measurement of spontaneous and therapeutic agent-induced apoptosis with BCL-2 protein expression in acute myeloid leukemia. Blood 89 (1): 243-55, 1997.[PUBMED Abstract]

Paietta EM, Neuberg D, Rowe JM, et al.: The prognostic significance of immuneprofiles in adult acute myeloid leukemia (AML) varies with age: a comparative analysis of the Eastern Cooperative Oncology Group (ECOG) database. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A13, 5a, 1997.

Banker DE, Groudine M, Appelbaum FR: Spontaneous and therapeutic agent-induced apoptosis with BCL-2 protein expression in acute myeloid leukemia. [Abstract] Blood 88 (10 suppl 1): A-2649, 665a, 1996.

Haferlach T, Bennett JM, Löffler H, et al.: Acute myeloid leukemia with translocation (8;21). Cytomorphology, dysplasia and prognostic factors in 41 cases. AML Cooperative Group and ECOG. Leuk Lymphoma 23 (3-4): 227-34, 1996.[PUBMED Abstract]

Kuss BJ, Deeley RG, Cole SP, et al.: The biological significance of the multidrug resistance gene MRP in inversion 16 leukemias. Leuk Lymphoma 20 (5-6): 357-64, 1996.[PUBMED Abstract]

Liu PP, Wijmenga C, Hajra A, et al.: Identification of the chimeric protein product of the CBFB-MYH11 fusion gene in inv(16) leukemia cells. Genes Chromosomes Cancer 16 (2): 77-87, 1996.[PUBMED Abstract]

Paietta EM, Andersen J, Yunis JJ, et al.: Immature acute monocytic leukemia (AMOL): blast cells expressing the interleukin-2 receptor b-chain and the stem cell factor receptor identify a new prognosis leukemic syndrome: an ECOG database study. [Abstract] Proceedings of the American Society of Clinical Oncology 15: A1057, 1996.

Secco C, Wiernik PH, Bennett JM, et al.: Acute leukemia with t(10;11)(p11-p15;q13-q23). Cancer Genet Cytogenet 86 (1): 31-4, 1996.[PUBMED Abstract]

Viswanatha DS, Chen IM, Liu PP, et al.: Characterization and rapid diagnostic utility of a novel antibody detecting the CBFBeta/SMMHC fusion protein of inversion (16)/t(16;16) associated with acute myeloid leukemia. [Abstract] Blood 88 (10 suppl 1): A-2646, 664a, 1996.

Paietta E, Andersen J, Rowe J, et al.: Myeloid blast cell maturation determines response in adult de novo acute myeloid leukemia (AML): a response-driven antigen expression analysis in 382 Eastern Cooperative Oncology Group (ECOG) patients. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-47, 86, 1995.

Slovak ML, Traweek ST, Willman CL, et al.: Trisomy 11: an association with stem/progenitor cell immunophenotype. Br J Haematol 90 (2): 266-73, 1995.[PUBMED Abstract]

Paietta E, Andersen J, Racevskis J, et al.: Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses. Leukemia 8 (6): 968-73, 1994.[PUBMED Abstract]

Downing JR, Head DR, Curcio-Brint AM, et al.: An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation. Blood 81 (11): 2860-5, 1993.[PUBMED Abstract]

Hunger SP, Tkachuk DC, Amylon MD, et al.: HRX involvement in de novo and secondary leukemias with diverse chromosome 11q23 abnormalities. Blood 81 (12): 3197-203, 1993.[PUBMED Abstract]

Rowe JM, Andersen JW, Cassileth PA, et al.: Post-remission therapy in adults with acute myelogenous leukemia: the Eastern Cooperative Oncology Group (ECOG) experience. Leukemia 6 (Suppl 4): 75-7, 1992.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Peter A. Cassileth, MD, Protocol chair (Contact information may not be current)
Ph: 305-243-4977

Southwest Oncology Group

Frederick Appelbaum, MD, Protocol chair
Ph: 206-288-1024
Email: fappelba@fhcrc.org

Cancer and Leukemia Group B

David Hurd, MD, Protocol chair
Ph: 336-716-2088; 800-446-2255
Email: dhurd@wfubmc.edu

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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