A Randomized Phase 2 Trial of Brentuximab Vedotin (SGN35, NSC# 749710), or Crizotinib (NSC#749005, Commercially Labeled) in Combination With Chemotherapy for Newly Diagnosed Patients With Anaplastic Large Cell Lymphoma (ALCL)

National Cancer Institute (NCI)154 个研究点分布在 1 个国家目标入组 137 人开始时间: 2013年11月13日最近更新: 2024年4月30日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 137
试验地点: 154
主要终点: Event Free Survival (EFS)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib and combination chemotherapy works in treating patients with newly diagnosed stage II-IV anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether brentuximab vedotin and combination chemotherapy is more effective than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.

详细描述

PRIMARY OBJECTIVES:

I. To determine the tolerability of brentuximab vedotin given in combination with standard chemotherapy (anaplastic large cell lymphoma [ALCL]99) and to determine the tolerability of crizotinib given in combination with chemotherapy (ALCL99).

II. To estimate the event free survival (EFS) of Arm brentuximab vedotin (BV) and Arm crizotinib (CZ) and contrast these to historical control data.

SECONDARY OBJECTIVES:

I. To determine the prognostic significance of minimal disseminated disease (MDD) at diagnosis and minimal residual disease (MRD) as measured by real-time (RT)-polymerase chain reaction (PCR) in peripheral blood.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: — 至 21 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Newly diagnosed patients with histologically proven ALCL (International Classification of Diseases for Oncology [ICD-0] code: 9714/3)
•Disease must be cluster of differentiation (CD)30 positive
•Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local institutional standards)
•Patients must have stage II, III, or IV disease
•Patients must have a life expectancy of >= 8 weeks
•Adequate Liver Function Defined As:
•Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
•Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is 45 U/L (within 7 days prior to enrollment)
•If the lab abnormality is thought to be due to the lymphoma the patient is eligible and dose adjustments should be made
•Adequate Cardiac Function Defined As:
•Shortening fraction of >= 27% by echocardiogram, or
•Ejection fraction of >= 50% by radionuclide angiogram
•Adequate Pulmonary Function Defined As:
•Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air unless current dysfunction is due to the lymphoma in which case the patient is eligible

排除标准

•Patients with central nervous system (CNS) disease are not eligible
•Patients with disease limited to the skin are not eligible, regardless of how wide-spread
•Patients with stage I disease are not eligible
•Patients who have received any prior cytotoxic chemotherapy for the current diagnosis of ALCL or any cancer diagnosed previously are not eligible
•Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass; emergent steroid treatment and/or radiation treatment should stop once protocol therapy is initiated
•Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL
•Female patients who are pregnant are not eligible; pregnancy tests must be obtained in girls who are post menarchal
•Lactating females are not eligible unless they have agreed not to breastfeed their infants
•Sexually active patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of treatment and for 3 months after stopping treatment
•Patients with Down syndrome are not eligible due to the amount of methotrexate and potential for side effects
•Patients with an immunodeficiency that existed prior to diagnosis such as primary immunodeficiency syndromes or organ transplant recipients are not eligible
•Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow therapeutic indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
•CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
•CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St. John's wort are not eligible; the topical use of these medications (if applicable) is allowed
•Patients that are known to be positive for human immunodeficiency virus (HIV) are not eligible; note: inclusion of HIV positive patients will be considered at a later date
•Patients who weigh < 10 kg are not eligible

研究组 & 干预措施

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5.

COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.

干预措施: Brentuximab Vedotin (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Cyclophosphamide (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Cytarabine (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Dexamethasone (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Doxorubicin Hydrochloride (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Etoposide (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Ifosfamide (Drug)

Arm BV (brentuximab vedotin, combination chemotherapy)

Experimental

干预措施: Methotrexate (Drug)