AzTrials
AzTrials

Recurrent Langerhans Cell HistiocytosisPhase 2NCT05828069

A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Langerhans Cell Histiocytosis and Refractory Langerhans Cell Histiocytosis, run by National Cancer Institute (NCI) at 123 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 180 days to 22 years
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
123 sitesin 3 countries
Study dates
28 Mar 2024to 30 Sep 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 180 days to 22 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

123 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

123 sites in 3 countries

United States108 sites, 103 recruiting

  • Albany Medical Center

    Albany, New York, 12208

    Site Public Contact, 518-262-5513

    Lauren R. Weintraub

    Recruiting

  • Mission Hospital

    Asheville, North Carolina, 28801

    Site Public Contact, 828-213-7055, NCDV.ResearchRegulatory@HCAHealthcare.com

    Douglas J. Scothorn

    Recruiting

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

    Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org

    Kathryn S. Sutton

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org

    Timothy P. Garrington

    Recruiting

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

    Site Public Contact, 512-628-1902, TXAUS-DL-SFCHemonc.research@ascension.org

    Shannon M. Cohn

    Recruiting

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

    Site Public Contact, 410-601-9083

    Jason M. Fixler

    Recruiting

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

    Site Public Contact, 410-955-8804, jhcccro@jhmi.edu

    Elias Zambidis

    Recruiting

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

    Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu

    Matthew A. Kutny

    Recruiting

  • Maimonides Medical Center

    Brooklyn, New York, 11219

    Site Public Contact, 718-765-2500

    Mahmut Y. Celiker

    Recruiting

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

    Site Public Contact, 304-388-9944, CAMCClinicalTrials@vandaliahealth.org

    Mohamad H. Badawi

    Recruiting

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

    Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu

    Brian C. Belyea

    Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

    Site Public Contact, 773-880-4562

    Joanna L. Weinstein

    Recruiting

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

    Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu

    Perry C. Morocco

    Recruiting

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

    Site Public Contact, 216-844-5437

    Duncan S. Stearns

    Recruiting

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

    Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org

    Stuart L. Cramer

    Recruiting

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

    Site Public Contact, 614-722-6039, Melinda.Triplet@nationwidechildrens.org

    Mark A. Ranalli

    Recruiting

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

    Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu

    Erin B. Butler

    Recruiting

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

    Site Public Contact, 570-271-5251, cancerresearch@geisinger.edu

    Jagadeesh Ramdas

    Recruiting

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

    Site Public Contact, 800-228-4055

    Jordan M. Wright

    Recruiting

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

    Site Public Contact, 303-832-2344, PSGResearchSharedMailbox@HCAHealthcare.com

    Florence Choo

    Recruiting

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

    Site Public Contact, 515-241-8912, samantha.mallory@unitypoint.org

    Samantha L. Mallory

    Recruiting

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

    Site Public Contact, 626-564-3455

    Robert M. Cooper

    Recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27710

    Site Public Contact, 888-275-3853

    Jessica M. Sun

    Recruiting

  • Michigan State University

    East Lansing, Michigan, 48823

    Suspended

  • El Paso Children's Hospital

    El Paso, Texas, 79905

    Site Public Contact, 915-298-5444, ranjan.bista@ttuhsc.edu

    Benjamin Carcamo

    Recruiting

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

    Site Public Contact, 239-343-5333, molly.arnstrom@leehealth.org

    Emad K. Salman

    Recruiting

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

    Site Public Contact, 352-273-8010

    Brian Stover

    Recruiting

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

    Site Public Contact, 920-433-8889, WI_research_admin@hshs.org

    Catherine A. Long

    Recruiting

  • East Carolina University

    Greenville, North Carolina, 27834

    Site Public Contact, 252-744-1015, eubankss@ecu.edu

    Andrea R. Whitfield

    Recruiting

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

    Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org

    Aniket Saha

    Recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Site Public Contact, 551-996-2897

    Katharine Offer

    Recruiting

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

    Site Public Contact, 860-545-9981

    Michael S. Isakoff

    Recruiting

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

    Site Public Contact, 954-265-1847, OHR@mhs.net

    Iftikhar Hanif

    Recruiting

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

    Site Public Contact, 808-983-6090

    Wade T. Kyono

    Recruiting

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 713-798-1354, burton@bcm.edu

    Olive S. Eckstein

    Recruiting

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 866-632-6789, askmdanderson@mdanderson.org

    Najat C. Daw

    Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

    Site Public Contact, 800-248-1199

    Jennifer A. Belsky

    Recruiting

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

    Site Public Contact, 800-237-1225

    Andrew P. Groves

    Recruiting

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

    Site Public Contact, 601-815-6700

    Amanda Strobel

    Recruiting

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Vibhuti Agarwal

    Recruiting

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

    Site Public Contact, 865-541-8266

    Susan E. Spiller

    Recruiting

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

    Site Public Contact, 702-384-0013, research@sncrf.org

    Joseph L. Lasky

    Recruiting

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

    Site Public Contact, 702-384-0013, research@sncrf.org

    Joseph L. Lasky

    Recruiting

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

    Site Public Contact, 859-257-3379

    James T. Badgett

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

    Site Public Contact, 501-364-7373

    Michael W. Bishop

    Recruiting

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

    Site Public Contact, 909-558-4050

    Albert Kheradpour

    Recruiting

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

    Site Public Contact, 562-933-5600

    Jacqueline N. Casillas

    Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

    Site Public Contact, 323-361-4110

    Rebecca S. Parker

    Recruiting

  • Valley Children's Hospital

    Madera, California, 93636

    Active, not recruiting

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

    Suspended

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

    Site Public Contact, 888-624-2778

    Ziad A. Khatib

    Recruiting

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

    Site Public Contact, 414-955-4727, MACCCTO@mcw.edu

    Peter H. Shaw

    Recruiting

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

    Site Public Contact, 612-813-5913, pauline.mitby@childrensmn.org

    Michael K. Richards

    Recruiting

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

    Active, not recruiting

  • Morristown Medical Center

    Morristown, New Jersey, 07960

    Site Public Contact, 973-971-5900

    Kathryn L. Laurie

    Recruiting

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

    Site Public Contact, 615-342-1919

    Clinton M. Carroll

    Recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

    Site Public Contact, 800-811-8480

    Devang J. Pastakia

    Recruiting

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

    Site Public Contact, 732-235-8675

    Marissa Botwinick

    Recruiting

  • Yale University

    New Haven, Connecticut, 06520

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Farzana Pashankar

    Recruiting

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

    Site Public Contact, 718-470-3460

    Julie I. Krystal

    Recruiting

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

    Site Public Contact, 504-894-5377

    Maria C. Velez-Yanguas

    Recruiting

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

    Site Public Contact, 504-842-8084, Elisemarie.curry@ochsner.org

    Craig Lotterman

    Recruiting

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

    Site Public Contact, CancerTrials@nyulangone.org

    Elizabeth A. Raetz

    Recruiting

  • Mount Sinai Hospital

    New York, New York, 10029

    Site Public Contact, 212-824-7309, CCTO@mssm.edu

    Pamela R. Merola

    Recruiting

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

    Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Nobuko Hijiya

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Christopher J. Forlenza

    Recruiting

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

    Site Public Contact, 212-746-1848

    Nitya Gulati

    Recruiting

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

    Site Public Contact, 757-668-7243, CCBDCresearch@chkd.org

    Melissa S. Mark

    Recruiting

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

    Site Public Contact, 510-428-3264, PedOncRschOAK@ucsf.edu

    Jennifer G. Michlitsch

    Recruiting

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

    Site Public Contact, 877-642-4691, Kpoct@kp.org

    Aarati V. Rao

    Recruiting

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

    Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu

    Rene Y. McNall-Knapp

    Recruiting

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

    Site Public Contact, 402-955-3949

    Jill C. Beck

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Site Public Contact, 402-559-6941, unmcrsa@unmc.edu

    Jill C. Beck

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, 92868

    Site Public Contact, 714-509-8646, oncresearch@choc.org

    Elyssa M. Rubin

    Recruiting

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

    Site Public Contact, 321-841-5357, Jennifer.spinelli@orlandohealth.com

    Zhongbo Hu

    Recruiting

  • Nemours Children's Hospital

    Orlando, Florida, 32827

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Vibhuti Agarwal

    Recruiting

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

    Site Public Contact, 800-694-0012, ccto-office@stanford.edu

    Jay Michael S. Balagtas

    Recruiting

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

    Site Public Contact, 973-754-2207, HallL@sjhmc.org

    Alissa Kahn

    Recruiting

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

    Site Public Contact, helpdesk@childrensoncologygroup.org

    Jeffrey H. Schwartz

    Recruiting

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

    Site Public Contact, 309-624-4945, ChildrensHospitalofIllinois@osfhealthcare.org

    Prerna Kumar

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu

    Michael D. Hogarty

    Recruiting

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

    Site Public Contact, 215-427-8991

    Gregory E. Halligan

    Recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

    Site Public Contact, 412-692-8570, jean.tersak@chp.edu

    Julia E. Segal

    Recruiting

  • Oregon Health and Science University

    Portland, Oregon, 97239

    Site Public Contact, 503-494-1080, trials@ohsu.edu

    Katrina Winsnes

    Recruiting

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

    Site Public Contact, 804-628-6430, CTOclinops@vcu.edu

    Nadirah El-Amin

    Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

    Site Public Contact, 801-585-5270

    Taumoha Ghosh

    Recruiting

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

    Site Public Contact, 210-704-2894, bridget.medina@christushealth.org

    Julie Voeller

    Recruiting

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

    Site Public Contact, 210-575-6240, Vinod.GidvaniDiaz@hcahealthcare.com

    Jose M. Esquilin

    Recruiting

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

    Site Public Contact, 210-450-3800, phoresearchoffice@uthscsa.edu

    Allison C. Grimes

    Recruiting

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

    Site Public Contact, 877-827-3222, cancertrials@ucsf.edu

    Natalie L. Wu

    Recruiting

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

    Site Public Contact, 912-350-7887, Lorraine.OHara@hcahealthcare.com

    James N. Yarnall

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Site Public Contact, 866-987-2000

    Sarah E. Leary

    Recruiting

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

    Site Public Contact, 605-312-3320, OncologyClinicalTrialsSF@SanfordHealth.org

    Jordan Fritch-Hanson

    Recruiting

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

    Site Public Contact, 800-228-6618, HopeBeginsHere@providence.org

    Judy L. Felgenhauer

    Recruiting

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

    Site Public Contact, 314-268-4000

    William S. Ferguson

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Bryan A. Sisk

    Recruiting

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

    Site Public Contact, 314-251-7066

    Robin D. Hanson

    Recruiting

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

    Site Public Contact, 727-767-4784, Ashley.Repp@jhmi.edu

    Jennifer B. Dean

    Recruiting

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

    Site Public Contact, 315-464-5476

    Melanie A. Comito

    Recruiting

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

    Site Public Contact, 813-357-0849, jennifer.manns@baycare.org

    Don E. Eslin

    Recruiting

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

    Site Public Contact, 254-724-5407

    Nicholas W. McGregor

    Recruiting

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Alice Lee

    Recruiting

  • New York Medical College

    Valhalla, New York, 10595

    Active, not recruiting

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

    Site Public Contact, 202-476-2800, OncCRC_OnCall@childrensnational.org

    Jeffrey S. Dome

    Recruiting

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Vibhuti Agarwal

    Recruiting

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

    Site Public Contact, 336-713-6771

    Sarah Supples

    Recruiting

Other trials in United States

Canada10 sites, 9 recruiting

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

    Site Public Contact, 780-407-8798, pedsoncologyresearch@ahs.ca

    Sarah J. McKillop

    Recruiting

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

    Site Public Contact, 902-470-8520, Research@iwk.nshealth.ca

    Chelsea Ash

    Recruiting

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

    Suspended

  • Children's Hospital

    London, Ontario, N6A 5W9

    Site Public Contact, 519-685-8306

    Shayna M. Zelcer

    Recruiting

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

    Site Public Contact, 514-412-4445, info@thechildren.com

    Stephanie Mourad

    Recruiting

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

    Site Public Contact, 514-345-4931, yvan.samson@umontreal.ca

    Monia Marzouki

    Recruiting

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

    Site Public Contact, 418-525-4444, rechclinique@crchudequebec.ulaval.ca

    Bruno Michon

    Recruiting

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec, J1H 5N4

    Site Public Contact, 819-820-6480, crcinformation.chus@ssss.gouv.qc.ca

    Stephanie Vairy

    Recruiting

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

    Site Public Contact, 416-813-7654, ask.CRS@sickkids.ca

    Oussama A. Abla

    Recruiting

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

    Site Public Contact, 604-875-2345 ext. 6477

    Rebecca J. Deyell

    Recruiting

Other trials in Canada

Australia5 sites, 5 recruiting

  • John Hunter Children's Hospital

    Hunter Regional Mail Centre, New South Wales, 2310

    Site Public Contact, (02) 4985 5180

    Kristy McCarthy

    Recruiting

  • Royal Children's Hospital

    Parkville, Victoria, 3052

    Site Public Contact, 61 3 9345 5656, Jordan.Hansford@rch.org.au

    Martin A. Campbell

    Recruiting

  • Perth Children's Hospital

    Perth, Western Australia, 6009

    Site Public Contact, helpdesk@childrensoncologygroup.org

    Michelle Ng

    Recruiting

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

    Site Public Contact, (02) 9382-1721

    Draga Barbaric

    Recruiting

  • Queensland Children's Hospital

    South Brisbane, Queensland, 4101

    Site Public Contact, 61 7 3068 1111

    Steven A. Foresto

    Recruiting

Other trials in Australia

About this study

Official title: Phase 2 Study of Tovorafenib (DAY101) in Relapsed and Refractory Langerhans Cell Histiocytosis

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Echocardiography Test
Medical subject headings
Histiocytosis, Langerhans-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood and urine samples

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FDG-Positron Emission Tomography and Computed Tomography ScanProcedure or surgery

    Also called FDG PET/CT

    Undergo FDG-PET imaging

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • TovorafenibDrug

    Also called BIIB 024, BIIB-024, BIIB024, DAY 101

    Given PO

Study groups in NCT05828069
Study groupRoleWhat they receive
Treatment (tovorafenib)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan; Procedure: Lumbar Puncture; Procedure: Multigated Acquisition Scan; Drug: Tovorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of dose limiting toxicity (dose finding phase)

    Will be analyzed descriptively.

    Measured: Up to 28 days

  2. Overall response rate (phase II)

    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.

    Measured: After 2 cycles of therapy (each cycle is 28 days)

Secondary outcomes (4)

  1. Event free survival rate

    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.

    Measured: At 1 and 2 years

  2. Progression free survival rate

    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.

    Measured: Up to 2 years

  3. Duration of response rate

    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.

    Measured: 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

  4. Overall survival rate

    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.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2023
  2. Study start28 Mar 2024
  3. Primary completion30 Sep 2028 (estimated)
  4. Study completion30 Sep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05828069
Sponsor's protocol ID
NCI-2022-06282
Other IDs
NCI-2022-06282, ANHL2121, ANHL2121, U10CA180886
Status last verified
Jul 2026
First submitted
21 Apr 2023
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Langerhans Cell Histiocytosis and Refractory Langerhans Cell Histiocytosis, run by National Cancer Institute (NCI) at 123 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 50 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 123 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of dose limiting toxicity (dose finding phase) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05828069.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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