Single Arm Romiplostim to Prevent CIT

Официальное название

Single Arm Evaluation of Romiplostim to Prevent Chemotherapy Induced Thrombocytopenia in Patients With Ewing Sarcoma

Обзор

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.

Подробное описание

This is a single-arm, multi-center clinical trial to assess the efficacy of romiplostim as a supportive care measure in patients with a new diagnosis of Ewing sarcoma receiving interval-compressed chemotherapy. Patients will be enrolled and started on romiplostim as early as cycle 1 day 1 of their chemotherapy, but no later than 2 weeks from the start of the 5th cycle. If their platelet count is \< 200,000/mm3, patients will start romiplostim based on their weight. Dose escalation of romiplostim may occur weekly if platelet count is \< 200,000/mm3. Once maximum dose of romiplostim is reached, this dose level will be maintained every 7 days (+/- 2 days).

Вмешательства

• Препарат Romiplostim (AMG-531)
  Romiplostim may be started as supportive care, as early as cycle 1 day 1; all patients MUST initiate romiplostim no later than 2 weeks from the start of the 5th cycle of chemotherapy (see exception below for patients with platelet count of 200,000 or greater). If plt count \< 200,000/mm3, patients will start romiplostim based on their weight

Первичные конечные точки

• Number of evaluable participants (11 or fewer of 26) that develop CIT during the continuation phase of compressed-interval chemotherapy compared to institutional historical control rate. [Срок оценки: 52 weeks]
• Measure adverse events with the addition of romiplostim when given with chemotherapy. [Срок оценки: 52 weeks]
• Number of patients able to receive the majority of planned romiplostim doses. [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• Age: Patients must be >1 year old at the time of study consent.
• Diagnosis: Patients with a new diagnosis of Ewing sarcoma treated with interval-compressed chemotherapy as per AEWS0031, AEWS1221, or AEWS1031.
• Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Критерии исключения

• Marrow disease: Patients with metastatic Ewing sarcoma to the bone marrow are not eligible. Marrow staging is not required for this study but should be performed if clinically indicated.
• Concomitant therapy, cancer directed: Patients receiving whole lung radiation, >50% of pelvic irradiation, other substantial bone marrow radiation (i.e. ≥ 50% of vertebral marrow space), or patients undergoing pneumonectomy as a component of local control before cycle 14, are not eligible. These therapies are not an exclusion if instituted during or after cycle 14.
• Concomitant therapy, non-cancer directed:

• Patients requiring hematopoietic stem cell rescue are not eligible.
• Previous use of romiplostim, eltrombopag or any other platelet-producing agent is not allowed.
• Previous therapy for immune thrombocytopenia and related conditions, including rituximab, mycophenolic acid, protracted systemic steroids, and/or IVIG, is prohibited.
• Treatment with erythropoietin-stimulating agents is prohibited.
• Patients receiving another investigational drug are not eligible.
• Patients who are receiving prophylactic dosing of heparin (i.e. enoxaparin) or oral anticoagulants (i.e. rivaroxaban) for thrombosis prevention may be considered for enrollment but will be excluded from secondary aim 'a' analysis (efficacy measured as the median platelet count and transfusion dependency) given shift in transfusion thresholds.
• Concurrent Illnesses: Patients with a history of or current diagnosis of bone marrow failure, hematologic malignancy, pro-thrombotic condition, or platelet disorder (including immune or heparin induced thrombocytopenia) are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the study (including safety monitoring requirements of the study) are not eligible.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

США · 2 центра

• Phoenix Children's — Phoenix
• Cincinnati Children's Hospital Medical Center — Cincinnati

Публикации

• 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. PMID 23091096
• 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. PMID 19245931
• 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. PMID 26811139
• 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. PMID 10741300
• 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. PMID 30764783
• 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 hematologic PMID 11205919
• 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 PMID 15606549
• 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 Grou PMID 15814645

Идентификаторы

NCT: NCT07048249 · Romiplostim-BT-2201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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