2157GCCC:Phase 1 of Calaspargase Pegol-mknl W/ Cytarabine and Idarubicin in Newly Dx AML

Summary

Characterizing the regimen limiting toxicity (RLT) of chemotherapeutic drug Calaspargase Pegol-mknl as remission induction and consolidation chemotherapy in patients with newly diagnosed Acute Myeloid Leukemia (AML) and Identifying the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Calaspargase Pegol-mknl.

Timeline

Start

2021-09-27

Primary completion

2025-12-31

Completion

2025-12-31

Publications

• Background Bade NA, Lu C, Patzke CL, Baer MR, Duong VH, Law JY, Lee ST, Sausville EA, Zimrin AB, Duffy AP, Lawson J, Emadi A. Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management. J Oncol Pharm Pract. 2020 Jan;26(1):74-92. doi: 10.1177/1078155219838316. Epub 2019 Mar 27.
• Background Freeman SD, Hourigan CS. MRD evaluation of AML in clinical practice: are we there yet? Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):557-569. doi: 10.1182/hematology.2019000060.
• Background 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.
• Background American Cancer Society. Key Statistics for AML. (2020).
• Background Lai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019 Sep 18;12(1):100. doi: 10.1186/s13045-019-0774-x.
• Background Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. doi: 10.1056/NEJMoa0904544.
• Background Emadi A, Zokaee H, Sausville EA. Asparaginase in the treatment of non-ALL hematologic malignancies. Cancer Chemother Pharmacol. 2014 May;73(5):875-83. doi: 10.1007/s00280-014-2402-3. Epub 2014 Feb 11.
• Background Emadi A, Law JY, Strovel ET, Lapidus RG, Jeng LJB, Lee M, Blitzer MG, Carter-Cooper BA, Sewell D, Van Der Merwe I, Philip S, Imran M, Yu SL, Li H, Amrein PC, Duong VH, Sausville EA, Baer MR, Fathi AT, Singh Z, Bentzen SM. Asparaginase Erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2018 Jan;81(1):217-222. doi: 10.1007/s00280-017-3459-6. Epub 2017 Nov 8.
• Background Emadi A. Exploiting AML vulnerability: glutamine dependency. Blood. 2015 Sep 10;126(11):1269-70. doi: 10.1182/blood-2015-07-659508. No abstract available.
• Background Willems L, Jacque N, Jacquel A, Neveux N, Maciel TT, Lambert M, Schmitt A, Poulain L, Green AS, Uzunov M, Kosmider O, Radford-Weiss I, Moura IC, Auberger P, Ifrah N, Bardet V, Chapuis N, Lacombe C, Mayeux P, Tamburini J, Bouscary D. Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3521-32. doi: 10.1182/blood-2013-03-493163. Epub 2013 Sep 6.
• Background Capizzi RL, Davis R, Powell B, Cuttner J, Ellison RR, Cooper MR, Dillman R, Major WB, Dupre E, McIntyre OR. Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia--a Cancer and Leukemia Group B Study. J Clin Oncol. 1988 Mar;6(3):499-508. doi: 10.1200/JCO.1988.6.3.499.
• Background Patzke CL, Duffy AP, Duong VH, El Chaer F, Trovato JA, Baer MR, Bentzen SM, Emadi A. Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia. J Clin Med. 2020 Feb 16;9(2):536. doi: 10.3390/jcm9020536.
• Background Angiolillo AL, Schore RJ, Devidas M, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Keilani T, Lane AR, Loh ML, Reaman GH, Adamson PC, Wood B, Wood C, Zheng HW, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children's Oncology Group Study AALL07P4. J Clin Oncol. 2014 Dec 1;32(34):3874-82. doi: 10.1200/JCO.2014.55.5763. Epub 2014 Oct 27.
• Background Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. doi: 10.1200/JCO.20.03692. Epub 2021 Jul 6.
• Background Li RJ, Jin R, Liu C, Cao X, Manning ML, Di XM, Przepiorka D, Namuswe F, Deisseroth A, Goldberg KB, Blumenthal GM, Pazdur R. FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in Children and Young Adults. Clin Cancer Res. 2020 Jan 15;26(2):328-331. doi: 10.1158/1078-0432.CCR-19-1255. Epub 2019 Aug 23.
• Background Li W, Gong X, Sun M, Zhao X, Gong B, Wei H, Mi Y, Wang J. High-dose cytarabine in acute myeloid leukemia treatment: a systematic review and meta-analysis. PLoS One. 2014 Oct 9;9(10):e110153. doi: 10.1371/journal.pone.0110153. eCollection 2014.
• Background Kern W, Estey EH. High-dose cytosine arabinoside in the treatment of acute myeloid leukemia: Review of three randomized trials. Cancer. 2006 Jul 1;107(1):116-24. doi: 10.1002/cncr.21543.
• Background Wetzler M, Andrews C, Ford LA, Tighe S, Barcos M, Sait SN, Block AW, Nowak NJ, Baer MR, Wang ES, Baumann H. Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia. Cancer. 2011 Nov 1;117(21):4861-8. doi: 10.1002/cncr.26097. Epub 2011 Mar 31.
• Background Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrere F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. doi: 10.1200/JCO.2013.51.8571. Epub 2013 Dec 2.
• Background Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996 Oct 15;88(8):2841-51.
• Background Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7.
• Background Chien WW, Le Beux C, Rachinel N, Julien M, Lacroix CE, Allas S, Sahakian P, Cornut-Thibaut A, Lionnard L, Kucharczak J, Aouacheria A, Abribat T, Salles G. Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines. Sci Rep. 2015 Jan 28;5:8068. doi: 10.1038/srep08068.
• Background Hutson RG, Kitoh T, Moraga Amador DA, Cosic S, Schuster SM, Kilberg MS. Amino acid control of asparagine synthetase: relation to asparaginase resistance in human leukemia cells. Am J Physiol. 1997 May;272(5 Pt 1):C1691-9. doi: 10.1152/ajpcell.1997.272.5.C1691.
• Background Richards NG, Kilberg MS. Asparagine synthetase chemotherapy. Annu Rev Biochem. 2006;75:629-54. doi: 10.1146/annurev.biochem.75.103004.142520.
• Background Aslanian AM, Fletcher BS, Kilberg MS. Asparagine synthetase expression alone is sufficient to induce l-asparaginase resistance in MOLT-4 human leukaemia cells. Biochem J. 2001 Jul 1;357(Pt 1):321-8. doi: 10.1042/0264-6021:3570321.
• Background Andrulis IL, Argonza R, Cairney AE. Molecular and genetic characterization of human cell lines resistant to L-asparaginase and albizziin. Somat Cell Mol Genet. 1990 Jan;16(1):59-65. doi: 10.1007/BF01650480.
• Background Aslanian AM, Kilberg MS. Multiple adaptive mechanisms affect asparagine synthetase substrate availability in asparaginase-resistant MOLT-4 human leukaemia cells. Biochem J. 2001 Aug 15;358(Pt 1):59-67. doi: 10.1042/0264-6021:3580059.
• Background Gallinetti J, Harputlugil E, Mitchell JR. Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR. Biochem J. 2013 Jan 1;449(1):1-10. doi: 10.1042/BJ20121098.
• Background Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer JM, Natt F, Bos JL, Zwartkruis FJ, Thomas G. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14238-43. doi: 10.1073/pnas.0506925102. Epub 2005 Sep 21.
• Background Emadi A, Kapadia B, Bollino D, Bhandary B, Baer MR, Niyongere S, Strovel ET, Kaizer H, Chang E, Choi EY, Ma X, Tighe KM, Carter-Cooper B, Moses BS, Civin CI, Mahurkar A, Shetty AC, Gartenhaus RB, Kamangar F, Lapidus RG. Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia. Leukemia. 2021 Jul;35(7):1907-1924. doi: 10.1038/s41375-020-01080-6. Epub 2020 Nov 16.
• Background FDA. CALASPARGASE PEGOL-MKNL FDA approval label <https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761102s000lbl.pdf> (2018).
• Background Ivanova A, Qaqish BF, Schell MJ. Continuous toxicity monitoring in phase II trials in oncology. Biometrics. 2005 Jun;61(2):540-5. doi: 10.1111/j.1541-0420.2005.00311.x.
• Background Horvath TD, Chan WK, Pontikos MA, Martin LA, Du D, Tan L, Konopleva M, Weinstein JN, Lorenzi PL. Assessment of l-Asparaginase Pharmacodynamics in Mouse Models of Cancer. Metabolites. 2019 Jan 9;9(1):10. doi: 10.3390/metabo9010010.

Drugs

Indications