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一项使用托伏拉非尼 (DAY101) 作为进行性、复发性或难治性朗格汉斯细胞组织细胞增生症治疗选择的研究

2026年10月29日 更新者：National Cancer Institute (NCI)

Tovorafenib (DAY101) 治疗复发难治性朗格汉斯细胞组织细胞增生症的 2 期研究

This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

PRIMARY OBJECTIVE:

I. To determine overall response rate (ORR) for children and young adults with relapsed or refractory BRAFV600E positive (cohort 1) and BRAFV600E negative (cohort 2) Langerhans cell histiocytosis (LCH) treated with tovorafenib (DAY101) after 2 cycles and must be maintained 4 weeks later.

SECONDARY OBJECTIVES:

I. To determine nature and severity of adverse events in patients treated with tovorafenib (DAY101) for relapsed or refractory LCH.

II. To describe event-free survival (EFS) at 1 year in children and young adults with relapsed and refractory LCH treated with tovorafenib (DAY 101) for up to 1 year.

III. To determine durability of response in children and young adults with relapsed or refractory LCH treated with tovorafenib (DAY101) following cessation of therapy in patients with complete response (CR) at 1 year.

IV. To describe progression-free (and relapse-free) survival (PFS) and overall survival (OS) in children and young adults with relapsed or refractory LCH treated with tovorafenib (DAY101) for up to 1 year.

EXPLORATORY OBJECTIVES:

I. To determine potential role of pathogenic tumor mutation in response to tovorafenib (DAY101), and to evaluate changes in bone marrow and peripheral blood cell populations carrying pathogenic mutations in response to tovorafenib (DAY101) therapy.

Ia. To define somatic mutations in LCH lesion biopsies; Ib. To determine impact of tovorafenib (DAY101) on bone marrow and blood BRAFV600E+ mononuclear cells; Ic. To determine impact of tovorafenib (DAY101) on cerebral spinal fluid and disease response; Id. To determine the performance of standardized immunohistochemical analysis of LCH lesion biopsies.

II. To compare performance of LCH-specific response criteria to Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

III. To describe the pharmacokinetics of tovorafenib (DAY101) when administered to pediatric and young adult patients with relapse or refractory LCH.

OUTLINE: This is a dose escalation study of tovorafenib followed by a phase II trial.

Patients receive tovorafenib orally (PO) once weekly (QW) on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-gated acquisition (MUGA) or echocardiography (ECHO) scans, and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) or computed tomography (CT) throughout the trial, and collection of blood and urine samples on study. Patients with suspicion of bone marrow and/or central nervous system involvement will also undergo bone marrow biopsy and aspiration and lumbar puncture on study and during follow up.

After completion of study treatment, patients are followed up at 28 days, months 3, 6, 9, and 12, and then at 2 years post cycle 12.

研究类型

介入性

注册 (估计的)

48

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 加拿大
      • Québec、加拿大、G1V 4G2
        • 招聘中
        • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
        • 首席研究员：
          • Bruno Michon
        • 接触：
    • Alberta
      • Edmonton、Alberta、加拿大、T6G 2B7
        • 招聘中
        • University of Alberta Hospital
        • 接触：
        • 首席研究员：
          • Sarah J. McKillop
    • British Columbia
      • Vancouver、British Columbia、加拿大、V6H 3V4
        • 招聘中
        • British Columbia Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：6477 604-875-2345
        • 首席研究员：
          • Rebecca J. Deyell
    • Nova Scotia
      • Halifax、Nova Scotia、加拿大、B3K 6R8
        • 招聘中
        • IWK Health Centre
        • 接触：
        • 首席研究员：
          • Chelsea Ash
    • Ontario
      • Hamilton、Ontario、加拿大、L8N 3Z5
        • 暂停
        • McMaster Children's Hospital at Hamilton Health Sciences
      • London、Ontario、加拿大、N6A 5W9
        • 招聘中
        • Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：519-685-8306
        • 首席研究员：
          • Shayna M. Zelcer
      • Toronto、Ontario、加拿大、M5G 1X8
        • 招聘中
        • Hospital for Sick Children
        • 接触：
        • 首席研究员：
          • Oussama A. Abla
    • Quebec
      • Montreal、Quebec、加拿大、H3H 1P3
        • 招聘中
        • The Montreal Children's Hospital of the MUHC
        • 接触：
        • 首席研究员：
          • Stephanie Mourad
      • Montreal、Quebec、加拿大、H3T 1C5
        • 招聘中
        • Centre Hospitalier Universitaire Sainte-Justine
        • 首席研究员：
          • Monia Marzouki
        • 接触：
      • Sherbrooke、Quebec、加拿大、J1H 5N4
        • 招聘中
        • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
        • 接触：
        • 首席研究员：
          • Stephanie Vairy
  • 澳大利亚
    • New South Wales
      • Hunter Regional Mail Centre、New South Wales、澳大利亚、2310
        • 招聘中
        • John Hunter Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：(02) 4985 5180
        • 首席研究员：
          • Kristy McCarthy
      • Randwick、New South Wales、澳大利亚、2031
        • 招聘中
        • Sydney Children's Hospital
        • 首席研究员：
          • Draga Barbaric
        • 接触：
          • Site Public Contact
          • 电话号码：(02) 9382-1721
    • Queensland
      • South Brisbane、Queensland、澳大利亚、4101
        • 招聘中
        • Queensland Children's Hospital
        • 首席研究员：
          • Steven A. Foresto
        • 接触：
          • Site Public Contact
          • 电话号码：61 7 3068 1111
    • Victoria
      • Parkville、Victoria、澳大利亚、3052
        • 招聘中
        • Royal Children's Hospital
        • 首席研究员：
          • Martin A. Campbell
        • 接触：
    • Western Australia
      • Perth、Western Australia、澳大利亚、6009
  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35233
        • 招聘中
        • Children's Hospital of Alabama
        • 接触：
        • 首席研究员：
          • Matthew A. Kutny
    • Arkansas
      • Little Rock、Arkansas、美国、72202-3591
        • 招聘中
        • Arkansas Children's Hospital
        • 首席研究员：
          • Michael W. Bishop
        • 接触：
          • Site Public Contact
          • 电话号码：501-364-7373
    • California
      • Downey、California、美国、90242
        • 招聘中
        • Kaiser Permanente Downey Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：626-564-3455
        • 首席研究员：
          • Robert M. Cooper
      • Loma Linda、California、美国、92354
        • 招聘中
        • Loma Linda University Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：909-558-4050
        • 首席研究员：
          • Albert Kheradpour
      • Long Beach、California、美国、90806
        • 招聘中
        • Miller Children's and Women's Hospital Long Beach
        • 接触：
          • Site Public Contact
          • 电话号码：562-933-5600
        • 首席研究员：
          • Jacqueline N. Casillas
      • Los Angeles、California、美国、90027
        • 招聘中
        • Children's Hospital Los Angeles
        • 接触：
          • Site Public Contact
          • 电话号码：323-361-4110
        • 首席研究员：
          • Rebecca S. Parker
      • Madera、California、美国、93636
        • 主动，不招人
        • Valley Children's Hospital
      • Oakland、California、美国、94611
        • 招聘中
        • Kaiser Permanente-Oakland
        • 接触：
          • Site Public Contact
          • 电话号码：877-642-4691
          • 邮箱：Kpoct@kp.org
        • 首席研究员：
          • Aarati V. Rao
      • Oakland、California、美国、94609
        • 招聘中
        • UCSF Benioff Children's Hospital Oakland
        • 首席研究员：
          • Jennifer G. Michlitsch
        • 接触：
      • Orange、California、美国、92868
        • 招聘中
        • Children's Hospital of Orange County
        • 接触：
        • 首席研究员：
          • Elyssa M. Rubin
      • Palo Alto、California、美国、94304
        • 招聘中
        • Lucile Packard Children's Hospital Stanford University
        • 接触：
        • 首席研究员：
          • Jay Michael S. Balagtas
      • San Francisco、California、美国、94158
        • 招聘中
        • UCSF Medical Center-Mission Bay
        • 接触：
        • 首席研究员：
          • Natalie L. Wu
    • Colorado
      • Aurora、Colorado、美国、80045
        • 招聘中
        • Children's Hospital Colorado
        • 接触：
        • 首席研究员：
          • Timothy P. Garrington
      • Denver、Colorado、美国、80218
        • 招聘中
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
        • 接触：
        • 首席研究员：
          • Florence Choo
    • Connecticut
      • Hartford、Connecticut、美国、06106
        • 招聘中
        • Connecticut Children's Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：860-545-9981
        • 首席研究员：
          • Michael S. Isakoff
      • New Haven、Connecticut、美国、06520
        • 招聘中
        • Yale University
        • 接触：
        • 首席研究员：
          • Farzana Pashankar
    • Delaware
      • Wilmington、Delaware、美国、19803
        • 招聘中
        • Alfred I duPont Hospital for Children
        • 接触：
        • 首席研究员：
          • Vibhuti Agarwal
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20010
        • 招聘中
        • Children's National Medical Center
        • 首席研究员：
          • Jeffrey S. Dome
        • 接触：
    • Florida
      • Fort Myers、Florida、美国、33908
        • 招聘中
        • Golisano Children's Hospital of Southwest Florida
        • 接触：
        • 首席研究员：
          • Emad K. Salman
      • Gainesville、Florida、美国、32610
        • 招聘中
        • UF Health Cancer Institute - Gainesville
        • 首席研究员：
          • Brian Stover
        • 接触：
          • Site Public Contact
          • 电话号码：352-273-8010
      • Hollywood、Florida、美国、33021
        • 招聘中
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：954-265-1847
          • 邮箱：OHR@mhs.net
        • 首席研究员：
          • Iftikhar Hanif
      • Jacksonville、Florida、美国、32207
        • 招聘中
        • Nemours Children's Clinic-Jacksonville
        • 接触：
        • 首席研究员：
          • Vibhuti Agarwal
      • Miami、Florida、美国、33155
        • 招聘中
        • Nicklaus Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：888-624-2778
        • 首席研究员：
          • Ziad A. Khatib
      • Miami、Florida、美国、33136
        • 暂停
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Orlando、Florida、美国、32806
        • 招聘中
        • Arnold Palmer Hospital for Children
        • 接触：
        • 首席研究员：
          • Zhongbo Hu
      • Orlando、Florida、美国、32827
        • 招聘中
        • Nemours Children's Hospital
        • 接触：
        • 首席研究员：
          • Vibhuti Agarwal
      • Pensacola、Florida、美国、32504
      • St. Petersburg、Florida、美国、33701
        • 招聘中
        • Johns Hopkins All Children's Hospital
        • 接触：
        • 首席研究员：
          • Jennifer B. Dean
      • Tampa、Florida、美国、33607
        • 招聘中
        • Saint Joseph's Hospital/Children's Hospital-Tampa
        • 接触：
        • 首席研究员：
          • Don E. Eslin
    • Georgia
      • Atlanta、Georgia、美国、30329
        • 招聘中
        • Children's Healthcare of Atlanta - Arthur M Blank Hospital
        • 首席研究员：
          • Kathryn S. Sutton
        • 接触：
      • Savannah、Georgia、美国、31404
        • 招聘中
        • Memorial Health University Medical Center
        • 接触：
        • 首席研究员：
          • James N. Yarnall
    • Hawaii
      • Honolulu、Hawaii、美国、96826
        • 招聘中
        • Kapiolani Medical Center for Women and Children
        • 接触：
          • Site Public Contact
          • 电话号码：808-983-6090
        • 首席研究员：
          • Wade T. Kyono
    • Illinois
      • Chicago、Illinois、美国、60611
        • 招聘中
        • Lurie Children's Hospital-Chicago
        • 接触：
          • Site Public Contact
          • 电话号码：773-880-4562
        • 首席研究员：
          • Joanna L. Weinstein
      • Chicago、Illinois、美国、60637
        • 招聘中
        • University of Chicago Comprehensive Cancer Center
        • 接触：
        • 首席研究员：
          • Perry C. Morocco
      • Peoria、Illinois、美国、61637
    • Indiana
      • Indianapolis、Indiana、美国、46202
        • 招聘中
        • Riley Hospital for Children
        • 接触：
          • Site Public Contact
          • 电话号码：800-248-1199
        • 首席研究员：
          • Jennifer A. Belsky
    • Iowa
      • Des Moines、Iowa、美国、50309
        • 招聘中
        • Blank Children's Hospital
        • 接触：
        • 首席研究员：
          • Samantha L. Mallory
      • Iowa City、Iowa、美国、52242
        • 招聘中
        • University of Iowa/Holden Comprehensive Cancer Center
        • 接触：
          • Site Public Contact
          • 电话号码：800-237-1225
        • 首席研究员：
          • Andrew P. Groves
    • Kentucky
      • Lexington、Kentucky、美国、40536
        • 招聘中
        • University of Kentucky/Markey Cancer Center
        • 接触：
          • Site Public Contact
          • 电话号码：859-257-3379
        • 首席研究员：
          • James T. Badgett
    • Louisiana
      • New Orleans、Louisiana、美国、70118
        • 招聘中
        • Children's Hospital New Orleans
        • 首席研究员：
          • Maria C. Velez-Yanguas
        • 接触：
          • Site Public Contact
          • 电话号码：504-894-5377
      • New Orleans、Louisiana、美国、70121
        • 招聘中
        • Ochsner Medical Center Jefferson
        • 接触：
        • 首席研究员：
          • Craig Lotterman
    • Maryland
      • Baltimore、Maryland、美国、21287
        • 招聘中
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • 接触：
        • 首席研究员：
          • Elias Zambidis
      • Baltimore、Maryland、美国、21215
        • 招聘中
        • Sinai Hospital of Baltimore
        • 首席研究员：
          • Jason M. Fixler
        • 接触：
          • Site Public Contact
          • 电话号码：410-601-9083
    • Michigan
      • East Lansing、Michigan、美国、48823
        • 暂停
        • Michigan State University
      • Grand Rapids、Michigan、美国、49503
        • 招聘中
        • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
        • 接触：
        • 首席研究员：
          • Kathleen Y. Butler
      • Kalamazoo、Michigan、美国、49007
        • 招聘中
        • Bronson Methodist Hospital
        • 接触：
        • 首席研究员：
          • Kathleen Y. Butler
    • Minnesota
      • Minneapolis、Minnesota、美国、55404
        • 招聘中
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
        • 首席研究员：
          • Michael K. Richards
        • 接触：
      • Minneapolis、Minnesota、美国、55455
        • 主动，不招人
        • University of Minnesota/Masonic Cancer Center
    • Mississippi
      • Jackson、Mississippi、美国、39216
        • 招聘中
        • University of Mississippi Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：601-815-6700
        • 首席研究员：
          • Amanda Strobel
    • Missouri
      • St Louis、Missouri、美国、63110
        • 招聘中
        • Washington University School of Medicine
        • 接触：
        • 首席研究员：
          • Bryan A. Sisk
      • St Louis、Missouri、美国、63141
        • 招聘中
        • Mercy Hospital Saint Louis
        • 接触：
          • Site Public Contact
          • 电话号码：314-251-7066
        • 首席研究员：
          • Robin D. Hanson
      • St Louis、Missouri、美国、63104
        • 招聘中
        • Cardinal Glennon Children's Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：314-268-4000
        • 首席研究员：
          • William S. Ferguson
    • Nebraska
      • Omaha、Nebraska、美国、68114
        • 招聘中
        • Children's Hospital and Medical Center of Omaha
        • 接触：
          • Site Public Contact
          • 电话号码：402-955-3949
        • 首席研究员：
          • Jill C. Beck
      • Omaha、Nebraska、美国、68198
        • 招聘中
        • University of Nebraska Medical Center
        • 接触：
        • 首席研究员：
          • Jill C. Beck
    • Nevada
      • Las Vegas、Nevada、美国、89135
        • 招聘中
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
        • 接触：
        • 首席研究员：
          • Joseph L. Lasky
      • Las Vegas、Nevada、美国、89144
        • 招聘中
        • Summerlin Hospital Medical Center
        • 接触：
        • 首席研究员：
          • Joseph L. Lasky
    • New Jersey
      • Hackensack、New Jersey、美国、07601
        • 招聘中
        • Hackensack University Medical Center
        • 首席研究员：
          • Katharine Offer
        • 接触：
          • Site Public Contact
          • 电话号码：551-996-2897
      • Morristown、New Jersey、美国、07960
        • 招聘中
        • Morristown Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：973-971-5900
        • 首席研究员：
          • Kathryn L. Laurie
      • New Brunswick、New Jersey、美国、08903
        • 招聘中
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
        • 首席研究员：
          • Marissa Botwinick
        • 接触：
          • Site Public Contact
          • 电话号码：732-235-8675
      • Paterson、New Jersey、美国、07503
        • 招聘中
        • Saint Joseph's Regional Medical Center
        • 接触：
        • 首席研究员：
          • Alissa Kahn
    • New York
      • Albany、New York、美国、12208
        • 招聘中
        • Albany Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：518-262-5513
        • 首席研究员：
          • Lauren R. Weintraub
      • Brooklyn、New York、美国、11219
        • 招聘中
        • Maimonides Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：718-765-2500
        • 首席研究员：
          • Mahmut Y. Celiker
      • New Hyde Park、New York、美国、11040
        • 招聘中
        • The Steven and Alexandra Cohen Children's Medical Center of New York
        • 接触：
          • Site Public Contact
          • 电话号码：718-470-3460
        • 首席研究员：
          • Julie I. Krystal
      • New York、New York、美国、10032
        • 招聘中
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • 首席研究员：
          • Nobuko Hijiya
        • 接触：
      • New York、New York、美国、10065
        • 招聘中
        • Memorial Sloan Kettering Cancer Center
        • 接触：
          • Site Public Contact
          • 电话号码：212-639-7592
        • 首席研究员：
          • Christopher J. Forlenza
      • New York、New York、美国、10016
        • 招聘中
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
        • 首席研究员：
          • Elizabeth A. Raetz
        • 接触：
      • New York、New York、美国、10029
        • 招聘中
        • Mount Sinai Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：212-824-7309
          • 邮箱：CCTO@mssm.edu
        • 首席研究员：
          • Pamela R. Merola
      • New York、New York、美国、10065
        • 招聘中
        • NYP/Weill Cornell Medical Center
        • 接触：
          • Site Public Contact
          • 电话号码：212-746-1848
        • 首席研究员：
          • Nitya Gulati
      • Syracuse、New York、美国、13210
        • 招聘中
        • State University of New York Upstate Medical University
        • 接触：
          • Site Public Contact
          • 电话号码：315-464-5476
        • 首席研究员：
          • Melanie A. Comito
      • The Bronx、New York、美国、10467
        • 招聘中
        • Montefiore Medical Center - Moses Campus
        • 接触：
        • 首席研究员：
          • Alice Lee
      • Valhalla、New York、美国、10595
        • 主动，不招人
        • New York Medical College
    • North Carolina
      • Asheville、North Carolina、美国、28801
      • Durham、North Carolina、美国、27710
        • 招聘中
        • Duke University Medical Center
        • 首席研究员：
          • Jessica M. Sun
        • 接触：
          • Site Public Contact
          • 电话号码：888-275-3853
      • Greenville、North Carolina、美国、27834
        • 招聘中
        • East Carolina University
        • 接触：
        • 首席研究员：
          • Andrea R. Whitfield
      • Winston-Salem、North Carolina、美国、27157
        • 招聘中
        • Wake Forest University Health Sciences
        • 接触：
          • Site Public Contact
          • 电话号码：336-713-6771
        • 首席研究员：
          • Sarah Supples
    • Ohio
      • Cleveland、Ohio、美国、44106
        • 招聘中
        • Rainbow Babies and Childrens Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：216-844-5437
        • 首席研究员：
          • Duncan S. Stearns
      • Columbus、Ohio、美国、43205
      • Dayton、Ohio、美国、45404
        • 招聘中
        • Dayton Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：800-228-4055
        • 首席研究员：
          • Jordan M. Wright
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73104
        • 招聘中
        • University of Oklahoma Health Sciences Center
        • 接触：
        • 首席研究员：
          • Rene Y. McNall-Knapp
    • Oregon
      • Portland、Oregon、美国、97239
        • 招聘中
        • Oregon Health and Science University
        • 接触：
        • 首席研究员：
          • Katrina Winsnes
    • Pennsylvania
      • Danville、Pennsylvania、美国、17822
        • 招聘中
        • Geisinger Medical Center
        • 首席研究员：
          • Jagadeesh Ramdas
        • 接触：
      • Philadelphia、Pennsylvania、美国、19104
        • 招聘中
        • Children's Hospital of Philadelphia
        • 首席研究员：
          • Michael D. Hogarty
        • 接触：
      • Philadelphia、Pennsylvania、美国、19134
        • 招聘中
        • Saint Christopher's Hospital for Children
        • 接触：
          • Site Public Contact
          • 电话号码：215-427-8991
        • 首席研究员：
          • Gregory E. Halligan
      • Pittsburgh、Pennsylvania、美国、15224
        • 招聘中
        • Children's Hospital of Pittsburgh of UPMC
        • 接触：
        • 首席研究员：
          • Julia E. Segal
    • South Carolina
      • Columbia、South Carolina、美国、29203
        • 招聘中
        • Prisma Health Richland Hospital
        • 首席研究员：
          • Stuart L. Cramer
        • 接触：
      • Greenville、South Carolina、美国、29605
        • 招聘中
        • BI-LO Charities Children's Cancer Center
        • 首席研究员：
          • Aniket Saha
        • 接触：
    • South Dakota
      • Sioux Falls、South Dakota、美国、57117-5134
    • Tennessee
      • Knoxville、Tennessee、美国、37916
        • 招聘中
        • East Tennessee Childrens Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：865-541-8266
        • 首席研究员：
          • Susan E. Spiller
      • Nashville、Tennessee、美国、37232
        • 招聘中
        • Vanderbilt University/Ingram Cancer Center
        • 接触：
          • Site Public Contact
          • 电话号码：800-811-8480
        • 首席研究员：
          • Devang J. Pastakia
      • Nashville、Tennessee、美国、37203
        • 招聘中
        • The Children's Hospital at TriStar Centennial
        • 接触：
          • Site Public Contact
          • 电话号码：615-342-1919
        • 首席研究员：
          • Clinton M. Carroll
    • Texas
      • Austin、Texas、美国、78723
      • Dallas、Texas、美国、75390
        • 招聘中
        • UT Southwestern/Simmons Cancer Center-Dallas
        • 接触：
        • 首席研究员：
          • Erin B. Butler
      • El Paso、Texas、美国、79905
        • 招聘中
        • El Paso Children's Hospital
        • 接触：
        • 首席研究员：
          • Benjamin Carcamo
      • Houston、Texas、美国、77030
        • 招聘中
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
        • 接触：
          • Site Public Contact
          • 电话号码：713-798-1354
          • 邮箱：burton@bcm.edu
        • 首席研究员：
          • Olive S. Eckstein
      • Houston、Texas、美国、77030
        • 招聘中
        • UT MD Anderson Cancer Center
        • 接触：
        • 首席研究员：
          • Najat C. Daw
      • San Antonio、Texas、美国、78207
        • 招聘中
        • Children's Hospital of San Antonio
        • 接触：
        • 首席研究员：
          • Julie Voeller
      • San Antonio、Texas、美国、78229
        • 招聘中
        • University of Texas Health Science Center at San Antonio
        • 接触：
        • 首席研究员：
          • Allison C. Grimes
      • San Antonio、Texas、美国、78229
        • 招聘中
        • Methodist Children's Hospital of South Texas
        • 接触：
        • 首席研究员：
          • Jose M. Esquilin
      • Temple、Texas、美国、76508
        • 招聘中
        • Scott and White Memorial Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：254-724-5407
        • 首席研究员：
          • Nicholas W. McGregor
    • Utah
      • Salt Lake City、Utah、美国、84113
        • 招聘中
        • Primary Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：801-585-5270
        • 首席研究员：
          • Taumoha Ghosh
    • Virginia
      • Charlottesville、Virginia、美国、22908
      • Norfolk、Virginia、美国、23507
        • 招聘中
        • Children's Hospital of The King's Daughters
        • 接触：
        • 首席研究员：
          • Melissa S. Mark
      • Richmond、Virginia、美国、23298
        • 招聘中
        • VCU Massey Comprehensive Cancer Center
        • 首席研究员：
          • Nadirah El-Amin
        • 接触：
    • Washington
      • Seattle、Washington、美国、98105
        • 招聘中
        • Seattle Children's Hospital
        • 接触：
          • Site Public Contact
          • 电话号码：866-987-2000
        • 首席研究员：
          • Sarah E. Leary
      • Spokane、Washington、美国、99204
        • 招聘中
        • Providence Sacred Heart Medical Center and Children's Hospital
        • 接触：
        • 首席研究员：
          • Judy L. Felgenhauer
    • West Virginia
      • Charleston、West Virginia、美国、25304
        • 招聘中
        • Vandalia Health/CAMC Institute for Academic Medicine
        • 首席研究员：
          • Mohamad H. Badawi
        • 接触：
    • Wisconsin
      • Green Bay、Wisconsin、美国、54301
        • 招聘中
        • Saint Vincent Hospital Cancer Center Green Bay
        • 首席研究员：
          • Catherine A. Long
        • 接触：
      • Milwaukee、Wisconsin、美国、53226
        • 招聘中
        • Children's Hospital of Wisconsin
        • 首席研究员：
          • Peter H. Shaw
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

5个月 至 22年 (孩子、成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • 180 days- < 22 years (at time of study enrollment)

  • Patient must have a body surface area of ≥ 0.3 m^2

  • Patients with progressive, relapsed, or recurrent LCH with measurable disease at study entry

    • Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry

      • Tissue confirmation of relapse is recommended but not required.
      • Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
      • Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
      • Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included

    • Patients must have measurable disease

    • Patients must have progressive or refractory disease or experience relapse after at least one previous systemic treatment strategy

    • Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient

  • Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube

  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16 years of age

  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

  • Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study

  • Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent or any other anticancer therapy (including MAPK pathway inhibitor) for at least 14 days prior to planned start of tovorafenib (DAY101)

  • Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT

  • Patients must have fully recovered from any prior surgery

  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, targeted inhibitor, and/or radiotherapy with toxicities reduced to grade 1 or less (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)

  • Steroids: =< 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible

  • Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation

  • Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation

  • Peripheral absolute neutrophil count (ANC) >= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

  • Platelet count >= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

  • Patients with marrow disease must have platelet count of >= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented

  • Hemoglobin >= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin >= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented

  • Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta [registered trademark]) or 7 days for short-acting growth factor

  • A serum creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

    • Age: 6 months to < 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
    • Age: 1 to < 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
    • Age: 2 to < 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
    • Age: 6 to < 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
    • Age: 10 to < 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
    • Age: 13 to < 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
    • Age: >= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
    • OR- a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2
    • OR- a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
    • Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility

  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

  • Alanine aminotransferase (ALT) =< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

  • Serum albumin >= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

  • For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease

  • Fractional shortening (FS) of >= 25% or ejection fraction of >= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)

  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH

  • Central Nervous System Function Defined As:

    • Patients with seizure disorder may be enrolled if well controlled
    • Central nervous system (CNS) toxicity =< Grade 2

  • Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication

  • All patients and/or their parent(s) or legal guardians must sign a written informed consent

  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion Criteria:

  • LCH arising along with other hematologic malignancy (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy

  • Disease scenarios as below will be excluded

    • Skin-limited disease
    • Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic biopsies only)
    • LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions

  • Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment

  • Refractory nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)

  • Uncontrolled systemic bacterial, viral, or fungal infection

  • Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)

  • History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease

  • Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible

  • History of solid organ or hematopoietic bone marrow transplantation

  • Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval > 440 ms based on triplicate electrocardiogram (ECG) average

  • History of Grade >= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry

  • History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components

  • CTCAE version (V.) 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation (> 5 x ULN)

  • Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of childbearing potential

  • Lactating females who plan to breastfeed their infants are ineligible

  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are ineligible. Women of childbearing potential must use non-hormonal contraception during tovorafenib treatment and for at least 28 days after the last dose. Men should use effective contraception and must not father a child while taking tovorafenib and for 14 days after the last dose

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Treatment (tovorafenib)

Patients receive tovorafenib PO QW on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO scans, and FDG-PET or CT throughout the trial, and collection of blood and urine samples on study. Patients with suspicion of bone marrow and/or central nervous system involvement will also undergo bone marrow biopsy and aspiration and lumbar puncture on study and during follow up.
程序：Bone Marrow Biopsy

Undergo bone marrow biopsy

其他名称：
  • 骨髓活检
  • 活组织检查，骨髓
程序：Computed Tomography

Undergo CT

其他名称：
  • CT
  • 猫
  • 电脑扫描
  • 计算机轴向断层扫描
  • 计算机断层扫描
  • CT扫描
  • 断层扫描
  • 计算机轴向断层扫描（程序）
  • 计算机断层扫描 (CT) 扫描
  • 诊断猫扫描
  • 诊断猫扫描服务类型
程序：Echocardiography Test

Undergo ECHO

其他名称：
  • 超声心动图
  • 欧共体
程序：Multigated Acquisition Scan

Undergo MUGA

其他名称：
  • 血池扫描
  • 平衡放射性核素血管造影
  • 门控血池成像
  • 穆加
  • 放射性核素脑室造影
  • 导航导航仪
  • 司马扫描
  • 同步多门采集扫描
  • 穆加扫描
  • 多门控采集扫描
  • 放射性核素脑室造影扫描
  • 门控心池扫描
  • RNV扫描
程序：Bone Marrow Aspiration

Undergo bone marrow aspiration

程序：Lumbar Puncture

Undergo lumbar puncture

其他名称：
  • 唱片
  • 脊柱穿刺
程序：Biospecimen Collection

Undergo collection of blood and urine samples

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
程序：FDG-Positron Emission Tomography and Computed Tomography Scan

Undergo FDG-PET imaging

其他名称：
  • 葡萄糖PET/CT
药品：Tovorafenib

Given PO

其他名称：
  • TAK-580
  • MLN2480
  • BIIB-024
  • 第101天
  • 第 101 天
  • DAY101
  • MLN-2480
  • 泛 RAF 激酶抑制剂 DAY101
  • TAK580
  • 奥杰姆达
  • BIIB 024
  • BIIB024
  • 马耳他语 2480
  • 泰克580

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Frequency of dose limiting toxicity (dose finding phase)
大体时间：Up to 28 days

Will be analyzed descriptively.
Up to 28 days
Overall response rate (phase II)
大体时间：After 2 cycles of therapy (each cycle is 28 days)

Will be assessed using minimax Simon's two-stage designs in each of the BRAFV600E and non-BRAFV600E cohorts separately. The two arms will not be directly compared. The 95% confidence interval for the overall response rate will be adjusted for the two-stage design.
After 2 cycles of therapy (each cycle is 28 days)

次要结果测量

结果测量
措施说明
大体时间
Event free survival rate
大体时间：At 1 and 2 years

Will be estimated by the Kaplan-Meier method beginning at study enrollment. Will be evaluated two years after enrollment of the last patient on the trial and estimates at specific timepoints will be presented along with log-log transformed 95% confidence intervals. Events are defined as relapse/progression, second malignant neoplasm, or death.
At 1 and 2 years
Progression free survival rate
大体时间：Up to 2 years

Will be estimated by the Kaplan-Meier method beginning at study enrollment. Will be evaluated by two years after enrollment of the last patient on the trial and estimates at specific timepoints will be presented along with log-log transformed 95% confidence intervals.
Up to 2 years
Duration of response rate
大体时间：After 12 months of therapy. From the scan confirming the complete response or partial response (whichever is recorded first), until the first occurrence of recurrent or progressive disease or death (event) or last known status on trial

Response is based on modified Response Evaluation Criteria for Solid Tumors (RECIST)/Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) consistent with other recent pediatric Langerhans Cell Histiocytosis trials (NCT02670707 and NCT04079179) and adult histiocytosis trials with MAPK inhibitors. Comparison of response assessed via RECIST versus (vs.) PERCIST will be analyzed by displaying two-way tables of the responses with no formal statistical testing.
After 12 months of therapy. From the scan confirming the complete response or partial response (whichever is recorded first), until the first occurrence of recurrent or progressive disease or death (event) or last known status on trial
Overall survival rate
大体时间：Up to 2 years

Will be estimated by the Kaplan-Meier method beginning at study enrollment. Will be evaluated two years after enrollment of the last patient on the trial and estimates at specific timepoints will be presented along with log-log transformed 95% confidence intervals.
Up to 2 years

其他结果措施

结果测量
措施说明
大体时间
Percent peripheral blood mononuclear cells with mutated allele
大体时间：Up to 2 years

Will be analyzed descriptively using logistic regression with complete response/progressive response vs. stable disease/progressive disease as the response variable.
Up to 2 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

National Cancer Institute (NCI)

调查人员

  • 首席研究员：Carl E Allen、Children's Oncology Group

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2024年3月28日

初级完成 (估计的)

2028年9月30日

研究完成 (估计的)

2028年9月30日

研究注册日期

首次提交

2023年4月21日

首先提交符合 QC 标准的

2023年4月21日

首次发布 (实际的)

2023年4月25日

研究记录更新

最后更新发布 (实际的)

2026年10月30日

上次提交的符合 QC 标准的更新

2026年10月29日

最后验证

2026年7月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • NCI-2022-06282
  • U10CA180886 (美国 NIH 拨款/合同)
  • ANHL2121 (其他标识符：CTEP)
  • NCI-2022-06282 (注册表标识符：CTRP (Clinical Trial Reporting Program))
  • ANHL2121 (其他标识符：Children's Oncology Group)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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