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
|Phase III||Treatment||Closed||16 to 55||NCI||E-3489|
CLB-9120, SWOG-9034, EST-3489, E3489
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.
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
Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy Prior hydroxyurea allowed Endocrine therapy: Prior corticosteroids allowed Radiotherapy: No prior radiotherapy Surgery: Not applicable
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
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.
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.
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]
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]
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.
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
Southwest Oncology Group
Cancer and Leukemia Group B
Ph: 336-716-2088; 800-446-2255
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.