Gemtuzumab Ozogamicin in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia Undergoing Remission Induction and Intensification Therapy

Summary

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as gemtuzumab ozogamicin, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. PURPOSE: This phase II trial is studying how well gemtuzumab ozogamicin works in treating young patients who are undergoing remission induction, intensification therapy, and allogeneic bone marrow transplant for newly diagnosed acute myeloid leukemia.

Timeline

Start

2003-12

Primary completion

2006-09

Completion

2013-12

Publications

• Background Pollard JA, Alonzo TA, Loken M, Gerbing RB, Ho PA, Bernstein ID, Raimondi SC, Hirsch B, Franklin J, Walter RB, Gamis A, Meshinchi S. Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood. 2012 Apr 19;119(16):3705-11. doi: 10.1182/blood-2011-12-398370. Epub 2012 Feb 29.
• Background Ho PA, Kopecky KJ, Alonzo TA, Gerbing RB, Miller KL, Kuhn J, Zeng R, Ries RE, Raimondi SC, Hirsch BA, Oehler V, Hurwitz CA, Franklin JL, Gamis AS, Petersdorf SH, Anderson JE, Godwin JE, Reaman GH, Willman CL, Bernstein ID, Radich JP, Appelbaum FR, Stirewalt DL, Meshinchi S. Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children's Oncology Group and SWOG. Blood. 2011 Oct 27;118(17):4561-6. doi: 10.1182/blood-2011-04-348888. Epub 2011 Aug 26.
• Background Ho PA, Kuhn J, Gerbing RB, Pollard JA, Zeng R, Miller KL, Heerema NA, Raimondi SC, Hirsch BA, Franklin JL, Lange B, Gamis AS, Alonzo TA, Meshinchi S. WT1 synonymous single nucleotide polymorphism rs16754 correlates with higher mRNA expression and predicts significantly improved outcome in favorable-risk pediatric acute myeloid leukemia: a report from the children's oncology group. J Clin Oncol. 2011 Feb 20;29(6):704-11. doi: 10.1200/JCO.2010.31.9327. Epub 2010 Dec 28.
• Background Ho PA, Alonzo TA, Kopecky KJ, Miller KL, Kuhn J, Zeng R, Gerbing RB, Raimondi SC, Hirsch BA, Oehler V, Hurwitz CA, Franklin JL, Gamis AS, Petersdorf SH, Anderson JE, Reaman GH, Baker LH, Willman CL, Bernstein ID, Radich JP, Appelbaum FR, Stirewalt DL, Meshinchi S. Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study. Leukemia. 2010 May;24(5):909-13. doi: 10.1038/leu.2010.56. Epub 2010 Apr 8.
• Background Ho PA, Zeng R, Alonzo TA, Gerbing RB, Miller KL, Pollard JA, Stirewalt DL, Heerema NA, Raimondi SC, Hirsch B, Franklin JL, Lange B, Meshinchi S. Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2010 Aug 5;116(5):702-10. doi: 10.1182/blood-2010-02-268953. Epub 2010 Apr 22.
• Background Phillips CL, Gerbing R, Alonzo T, Perentesis JP, Harley IT, Meshinchi S, Bhatla D, Radloff G, Davies SM. MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Aug;55(2):248-53. doi: 10.1002/pbc.22519.
• Background Pollard JA, Alonzo TA, Gerbing RB, Ho PA, Zeng R, Ravindranath Y, Dahl G, Lacayo NJ, Becton D, Chang M, Weinstein HJ, Hirsch B, Raimondi SC, Heerema NA, Woods WG, Lange BJ, Hurwitz C, Arceci RJ, Radich JP, Bernstein ID, Heinrich MC, Meshinchi S. Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood. 2010 Mar 25;115(12):2372-9. doi: 10.1182/blood-2009-09-241075. Epub 2010 Jan 7.
• Background Berman JN, Gerbing RB, Alonzo TA, Ho PA, Miller K, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Gamis A, Meshinchi S. Prevalence and clinical implications of NRAS mutations in childhood AML: a report from the Children's Oncology Group. Leukemia. 2011 Jun;25(6):1039-42. doi: 10.1038/leu.2011.31. Epub 2011 Mar 1. No abstract available.
• Background Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Radich JP, Meshinchi S. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2009 Jun 25;113(26):6558-66. doi: 10.1182/blood-2008-10-184747. Epub 2009 Mar 20.
• Background Sung L, Alonzo TA, Gerbing RB, Aplenc R, Lange BJ, Woods WG, Feusner J, Franklin J, Patterson MJ, Gamis AS; Children's Oncology Group. Respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2008 Dec;51(6):784-6. doi: 10.1002/pbc.21710.
• Background Pollard J, Alonzo T, Gerbing R, et al.: Prevalence and prognostic significance of c-KIT mutations in pediatric CBF AML patients enrolled on serial CCG/COG protocols. [Abstract] Blood 110 (11): A-1442, 2007.
• Results Cooper TM, Franklin J, Gerbing RB, Alonzo TA, Hurwitz C, Raimondi SC, Hirsch B, Smith FO, Mathew P, Arceci RJ, Feusner J, Iannone R, Lavey RS, Meshinchi S, Gamis A. AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: a report from the Children's Oncology Group. Cancer. 2012 Feb 1;118(3):761-9. doi: 10.1002/cncr.26190. Epub 2011 Jul 15.
• Results Gudgeon CJ, Harrington KH, Laszlo GS, Alonzo TA, Gerbing RB, Gamis AS, Raimondi SC, Hirsch BA, Meshinchi S, Walter RB. High expression of neutrophil elastase predicts improved survival in pediatric acute myeloid leukemia: a report from the Children's Oncology Group. Leuk Lymphoma. 2013 Jan;54(1):202-4. doi: 10.3109/10428194.2012.700480. Epub 2012 Jul 9. No abstract available.
• Results Loken MR, Alonzo TA, Pardo L, Gerbing RB, Raimondi SC, Hirsch BA, Ho PA, Franklin J, Cooper TM, Gamis AS, Meshinchi S. Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children's Oncology Group. Blood. 2012 Aug 23;120(8):1581-8. doi: 10.1182/blood-2012-02-408336. Epub 2012 May 30.
• Results Ho PA, Kutny MA, Alonzo TA, Gerbing RB, Joaquin J, Raimondi SC, Gamis AS, Meshinchi S. Leukemic mutations in the methylation-associated genes DNMT3A and IDH2 are rare events in pediatric AML: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Aug;57(2):204-9. doi: 10.1002/pbc.23179. Epub 2011 Apr 18.
• Results Walter RB, Alonzo TA, Gerbing RB, Ho PA, Smith FO, Raimondi SC, Hirsch BA, Gamis AS, Franklin JL, Hurwitz CA, Loken MR, Meshinchi S. High expression of the very late antigen-4 integrin independently predicts reduced risk of relapse and improved outcome in pediatric acute myeloid leukemia: a report from the children's oncology group. J Clin Oncol. 2010 Jun 10;28(17):2831-8. doi: 10.1200/JCO.2009.27.5693. Epub 2010 Apr 26.
• Results Walter RB, Alonzo TA, Gerbing RB, et al.: High expression of the very late antigen (VLA)-4 (CD49d) integrin predicts for reduced risk of relapse and better outcome in pediatric acute myeloid leukemia (AML): A report from the Children's Oncology Group. [Abstract] Blood 114 (22): A-1592, 2009.
• Results Franklin J, Alonzo T, Hurwitz CA, et al.: COG AAML03P1: efficacy and safety in a pilot study of intensive chemotherapy including gemtuzumab in children newly diagnosed with acute myeloid leukemia (AML). [Abstract] Blood 112 (11): A- 136, 2008.
• Scheidegger N, Schneider C, Alexe G, Wang YC, Alonzo TA, Basanthakumar A, Bourgeois WA, Dudkiewicz-Garbicz J, Khalid D, Merickel LA, Perry JA, Ries RE, Salhotra S, Taillon A, Gamis A, Aplenc R, Harris MH, Wunderlich M, Armstrong SA, Pollard JA, Meshinchi S, Pikman Y, Stegmaier K. Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia. Blood Adv. 2026 Jul 14;10(13):4757-4771. doi: 10.1182/bloodadvances.2025016208.
• Tarlock K, Gerbing RB, Ries RE, Smith JL, Leonti A, Huang BJ, Kirkey D, Robinson L, Peplinski JH, Lange B, Cooper TM, Gamis AS, Kolb EA, Aplenc R, Pollard JA, Alonzo TA, Meshinchi S. Prognostic impact of cooccurring mutations in FLT3-ITD pediatric acute myeloid leukemia. Blood Adv. 2024 May 14;8(9):2094-2103. doi: 10.1182/bloodadvances.2023011980.
• Zarnegar-Lumley S, Alonzo TA, Gerbing RB, Othus M, Sun Z, Ries RE, Wang J, Leonti A, Kutny MA, Ostronoff F, Radich JP, Appelbaum FR, Pogosova-Agadjanyan EL, O'Dwyer K, Tallman MS, Litzow M, Atallah E, Cooper TM, Aplenc RA, Abdel-Wahab O, Gamis AS, Luger S, Erba H, Levine R, Kolb EA, Stirewalt DL, Meshinchi S, Tarlock K. Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis. Blood Adv. 2023 Oct 10;7(19):5941-5953. doi: 10.1182/bloodadvances.2022008282.
• Bertrums EJM, Smith JL, Harmon L, Ries RE, Wang YJ, Alonzo TA, Menssen AJ, Chisholm KM, Leonti AR, Tarlock K, Ostronoff F, Pogosova-Agadjanyan EL, Kaspers GJL, Hasle H, Dworzak M, Walter C, Muhlegger N, Morerio C, Pardo L, Hirsch B, Raimondi S, Cooper TM, Aplenc R, Gamis AS, Kolb EA, Farrar JE, Stirewalt D, Ma X, Shaw TI, Furlan SN, Brodersen LE, Loken MR, Van den Heuvel-Eibrink MM, Zwaan CM, Triche TJ, Goemans BF, Meshinchi S. Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. Haematologica. 2023 Aug 1;108(8):2044-2058. doi: 10.3324/haematol.2022.281653.
• Vujkovic M, Attiyeh EF, Ries RE, Goodman EK, Ding Y, Kavcic M, Alonzo TA, Wang YC, Gerbing RB, Sung L, Hirsch B, Raimondi S, Gamis AS, Meshinchi S, Aplenc R. Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report. Blood. 2017 Jun 8;129(23):3051-3058. doi: 10.1182/blood-2017-03-772384. Epub 2017 Apr 14.

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Indications