Single Arm Romiplostim to Prevent CIT

Summary

The goal of this clinical trial is to to assess the efficacy of romiplostim as a supportive care measure in patients with a new diagnosis of Ewing sarcoma receiving interval-compressed chemotherapy. The main questions it aims to answer are: 1. To demonstrate the efficacy of romiplostim in patients with newly diagnosed Ewing sarcoma, measured specifically as the rate of CIT, defined as a failure to achieve platelet recovery (≥ 75,000/µL post nadir, without transfusion, or a platelet count sufficient to resume chemotherapy per provider and institutional standard) within 7 days of planned chemotherapy cycle start, measured during the continuation phase (cycle 7 to end of cycle 13 or 16, per AEWS0031/AEWS1221, or AEWS1031 respectively) of interval-compressed chemotherapy (every 2 week vincristine/cyclophosphamide +/- doxorubicin and ifosfamide/etoposide chemotherapy) as compared to published institutional historical control rate. 2. To determine the safety of incorporation of romiplostim supportive care when given concurrently with Ewing sarcoma therapy. 3. To determine the feasibility of incorporation of romiplostim supportive care into upfront Ewing sarcoma regimens.

Timeline

Start

2024-01-26

Primary completion

2027-01-01

Completion

2028-01-01

Publications

• Background Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, Weiss AR. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-54. doi: 10.1200/JCO.2011.41.5703. Epub 2012 Oct 22.
• Background Vadhan-Raj S. Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents. Semin Hematol. 2009 Jan;46(1 Suppl 2):S26-32. doi: 10.1053/j.seminhematol.2008.12.007.
• Background Tamamyan G, Danielyan S, Lambert MP. Chemotherapy induced thrombocytopenia in pediatric oncology. Crit Rev Oncol Hematol. 2016 Mar;99:299-307. doi: 10.1016/j.critrevonc.2016.01.005. Epub 2016 Jan 15.
• Background Womer RB, Daller RT, Fenton JG, Miser JS. Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing's sarcomas and soft tissue sarcomas in children. Eur J Cancer. 2000 Jan;36(1):87-94. doi: 10.1016/s0959-8049(99)00236-1.
• Background Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D. Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5.
• Background Bracho F, Krailo MD, Shen V, Bergeron S, Davenport V, Liu-Mares W, Blazar BR, Panoskaltsis-Mortari A, van de Ven C, Secola R, Ames MM, Reid JM, Reaman GH, Cairo MS. A phase I clinical, pharmacological, and biological trial of interleukin 6 plus granulocyte-colony stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent/refractory solid tumors: enhanced hematological responses but a high incidence of grade III/IV constitutional toxicities. Clin Cancer Res. 2001 Jan;7(1):58-67.
• Background Cairo MS, Davenport V, Bessmertny O, Goldman SC, Berg SL, Kreissman SG, Laver J, Shen V, Secola R, van de Ven C, Reaman GH. Phase I/II dose escalation study of recombinant human interleukin-11 following ifosfamide, carboplatin and etoposide in children, adolescents and young adults with solid tumours or lymphoma: a clinical, haematological and biological study. Br J Haematol. 2005 Jan;128(1):49-58. doi: 10.1111/j.1365-2141.2004.05281.x.
• Background Angiolillo AL, Davenport V, Bonilla MA, van de Ven C, Ayello J, Militano O, Miller LL, Krailo M, Reaman G, Cairo MS; Children's Oncology Group. A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a Children's Oncology Group experience. Clin Cancer Res. 2005 Apr 1;11(7):2644-50. doi: 10.1158/1078-0432.CCR-04-1959.
• Background Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood. 2001 Dec 1;98(12):3241-8. doi: 10.1182/blood.v98.12.3241.
• Background Kuter DJ. Milestones in understanding platelet production: a historical overview. Br J Haematol. 2014 Apr;165(2):248-58. doi: 10.1111/bjh.12781. Epub 2014 Feb 14.
• Background Zhang J, Liang Y, Ai Y, Xie J, Li Y, Zheng W. Thrombopoietin-receptor agonists for children with immune thrombocytopenia: a systematic review. Expert Opin Pharmacother. 2017 Oct;18(15):1543-1551. doi: 10.1080/14656566.2017.1373091. Epub 2017 Sep 4.
• Background Tumaini Massaro J, Chen Y, Ke Z. Efficacy and safety of thrombopoietin receptor agonists in children with chronic immune thrombocytopenic purpura: meta-analysis. Platelets. 2019;30(7):828-835. doi: 10.1080/09537104.2019.1572873. Epub 2019 Feb 27.
• Background Bowers C, Mytych DT, Lawrence T, Wang K, Barger TE, Eisen M, Bennett CM, Tarantino MD. Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry. Blood Adv. 2021 Dec 14;5(23):4969-4979. doi: 10.1182/bloodadvances.2021005105.
• Background Mones JV, Soff G. Management of Thrombocytopenia in Cancer Patients. Cancer Treat Res. 2019;179:139-150. doi: 10.1007/978-3-030-20315-3_9.
• Background Al-Samkari H, Soff GA. Clinical challenges and promising therapies for chemotherapy-induced thrombocytopenia. Expert Rev Hematol. 2021 May;14(5):437-448. doi: 10.1080/17474086.2021.1924053. Epub 2021 May 13.
• Background Jacobson AE, Shah N, Setty BA. Romiplostim for therapy-related thrombocytopenia in pediatric malignancies. Pediatr Blood Cancer. 2017 Aug;64(8). doi: 10.1002/pbc.26473. Epub 2017 Feb 2.
• Background Merjaneh N, Young J, Mangoli A, Olsen M, Setty B, Lane A, Nagarajan R, Pressey JG, Turpin B. Chemotherapy-induced thrombocytopenia in Ewing sarcoma: Implications and potential for romiplostim supportive care. Pediatr Blood Cancer. 2022 Jul;69(7):e29548. doi: 10.1002/pbc.29548. Epub 2021 Dec 28.
• Background Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. doi: 10.1016/S0140-6736(16)00279-8. Epub 2016 Apr 18.
• Background Al-Samkari H, Kuter DJ. Thrombopoietin level predicts response to treatment with eltrombopag and romiplostim in immune thrombocytopenia. Am J Hematol. 2018 Dec;93(12):1501-1508. doi: 10.1002/ajh.25275. Epub 2018 Sep 26.
• Background Song AB, Goodarzi K, Karp Leaf R, Kuter DJ, Al-Samkari H. Thrombopoietin level predicts response to treatment with romiplostim in chemotherapy-induced thrombocytopenia. Am J Hematol. 2021 Dec 1;96(12):1563-1568. doi: 10.1002/ajh.26338. Epub 2021 Sep 10.
• Background Xie Z, Zeidan AM. CHIPing away the progression potential of CHIP: A new reality in the making. Blood Rev. 2023 Mar;58:101001. doi: 10.1016/j.blre.2022.101001. Epub 2022 Aug 15.
• Background Giagounidis A, Mufti GJ, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, Gaidano G, Wiktor-Jedrzejczak W, Hu K, Woodard P, Yang AS, Kantarjian HM. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer. 2014 Jun 15;120(12):1838-46. doi: 10.1002/cncr.28663. Epub 2014 Apr 4.
• Background Vishnu P, Aboulafia DM. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia. J Blood Med. 2016 May 25;7:99-106. doi: 10.2147/JBM.S80646. eCollection 2016.
• Background Wilkins CR, Ortiz J, Gilbert LJ, Yin S, Mones JV, Parameswaran R, Mantha S, Soff GA. Romiplostim for chemotherapy-induced thrombocytopenia: Efficacy and safety of extended use. Res Pract Thromb Haemost. 2022 May 10;6(3):e12701. doi: 10.1002/rth2.12701. eCollection 2022 Mar.
• Background Soff GA, Miao Y, Bendheim G, Batista J, Mones JV, Parameswaran R, Wilkins CR, Devlin SM, Abou-Alfa GK, Cercek A, Kemeny NE, Sarasohn DM, Mantha S. Romiplostim Treatment of Chemotherapy-Induced Thrombocytopenia. J Clin Oncol. 2019 Nov 1;37(31):2892-2898. doi: 10.1200/JCO.18.01931. Epub 2019 Sep 23.
• Background Al-Samkari H, Parnes AD, Goodarzi K, Weitzman JI, Connors JM, Kuter DJ. A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies. Haematologica. 2021 Apr 1;106(4):1148-1157. doi: 10.3324/haematol.2020.251900.
• Background Paz-Priel I, Long L, Helman LJ, Mackall CL, Wayne AS. Thromboembolic events in children and young adults with pediatric sarcoma. J Clin Oncol. 2007 Apr 20;25(12):1519-24. doi: 10.1200/JCO.2006.06.9930.
• Background Athale U, Cox S, Siciliano S, Chan AK. Thromboembolism in children with sarcoma. Pediatr Blood Cancer. 2007 Aug;49(2):171-6. doi: 10.1002/pbc.21047.

Drugs

Indications