Actively Recruiting
Phase 2 Study of Tovorafenib (DAY101) for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis in Children and Young Adults
Led by National Cancer Institute (NCI) · Updated on 2026-06-05
48
Participants Needed
117
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, side effects, best dose, and activity of tovorafenib (DAY101) in treating children and young adults with progressive, relapsed, or refractory Langerhans cell histiocytosis (LCH), a disease where too many immature Langerhans cells build up and form tumors in organs like bones, skin, lungs, and pituitary gland. This phase II trial focuses on patients whose disease is growing, spreading, or returning after prior treatment. The study aims to understand how well tovorafenib works and its effects on patients with different genetic mutations related to LCH. Participants receive tovorafenib orally once a week on days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles unless the disease worsens or side effects are unacceptable. Throughout the trial, patients undergo imaging scans such as MUGA or echocardiography and FDG-PET or CT to monitor disease status. Blood and urine samples are collected regularly. Those suspected of having bone marrow or central nervous system involvement will also have bone marrow biopsies, aspirations, and lumbar punctures during the study and follow-up. Patients are involved in regular assessments including scans, laboratory tests, and sample collections to monitor response and safety. Follow-up visits occur 28 days after treatment ends, then at 3, 6, 9, and 12 months, and finally 2 years after completing treatment. The main measures include overall response rate after 2 cycles, event-free survival, progression-free survival, duration of response, and overall survival, with safety monitored continuously throughout the trial.
CONDITIONS
Brief Title
A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 180 days and under 22 years at enrollment
- Body surface area of at least 0.3 m^2
- Diagnosis of progressive, relapsed, or recurrent Langerhans cell histiocytosis with measurable disease
- Histologic verification of LCH from original diagnosis or relapse/progression
- Pathogenic somatic mutation detected in specified genes related to LCH
- Ability to take oral or enteral medication (oral suspension or tablet)
- Karnofsky or Lansky performance status of 50% or higher
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- No myelosuppressive chemotherapy or investigational anticancer therapy within 14 days prior to study
- No radiation therapy within 2 weeks after last dose fraction
- Fully recovered from prior surgery and acute toxic effects of prior therapies
- Steroid use of 0.5 mg/kg/day prednisone equivalent or less averaged over the month prior
- No use of strong CYP2C8 inducers or inhibitors 14 days before and during study
- No use of certain narrow therapeutic index BCRP substrate medications 14 days before and during study
- Adequate blood counts and organ function as specified
- Fractional shortening of 25% or greater or ejection fraction of 50% or greater within 28 days prior
- No dyspnea at rest or exercise intolerance unless due to pulmonary LCH
- Controlled seizure disorder if present
- HIV patients on effective antiviral therapy without interfering medications
- Signed informed consent and compliance with all regulatory requirements
You will not qualify if you...
- LCH with other hematologic malignancies or history of non-histiocytic cancers
- Skin-limited disease or GI tract involvement only by endoscopic biopsy
- LCH-associated neurodegeneration without parenchymal or systemic lesions
- Activating mutations in MAP2K1 gene
- Refractory nausea, vomiting, malabsorption, or external biliary shunt
- Uncontrolled infections
- Major surgery or significant trauma within 14 days prior to enrollment
- History of significant bowel resection or malabsorptive disease
- Significant ophthalmologic conditions or risk factors for retinal vein occlusion or central serous retinopathy
- History of organ or bone marrow transplant
- Active cardiovascular disease or recent serious cardiac events
- History of significant central nervous system hemorrhage
- Allergy to tovorafenib or severe drug reaction history
- Grade 3 symptomatic creatinine kinase elevation
- Pregnant or breastfeeding females
- Patients not agreeing to use effective contraception during and after study participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - Up to 12 months (12 cycles of 28 days each)
Participants receive tovorafenib orally once weekly on days 1, 8, 15, and 22 of each 28-day cycle. This continues for up to 12 cycles unless there is disease progression or unacceptable side effects. Participants will also undergo heart scans (MUGA or ECHO), imaging scans (FDG-PET or CT), and provide blood and urine samples during this time. Those suspected of bone marrow or central nervous system involvement will have additional biopsies and lumbar punctures performed during the study.
Weekly visits for each dose during 28-day cycles, with imaging and sample collection visits throughout treatment
Duration - Up to 2 years post treatment
After completing treatment, participants are monitored with follow-up visits to assess their health and response to therapy. Additional biopsies and lumbar punctures may be performed if needed.
Visits at 28 days, then at months 3, 6, 9, 12, and 24 after treatment completion
Trial Site Locations
Total: 117 locations
1
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
Actively Recruiting
2
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202-3591
Actively Recruiting
3
Kaiser Permanente Downey Medical Center
Downey, California, United States, 90242
Actively Recruiting
4
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Actively Recruiting
5
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Actively Recruiting
6
Valley Children's Hospital
Madera, California, United States, 93636
Active, Not Recruiting
7
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States, 94609
Actively Recruiting
8
Kaiser Permanente-Oakland
Oakland, California, United States, 94611
Actively Recruiting
9
Children's Hospital of Orange County
Orange, California, United States, 92868
Actively Recruiting
10
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Actively Recruiting
11
UCSF Medical Center-Mission Bay
San Francisco, California, United States, 94158
Actively Recruiting
12
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Actively Recruiting
13
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, United States, 80218
Actively Recruiting
14
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
Actively Recruiting
15
Yale University
New Haven, Connecticut, United States, 06520
Actively Recruiting
16
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
Actively Recruiting
17
Children's National Medical Center
Washington D.C., District of Columbia, United States, 20010
Actively Recruiting
18
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States, 33908
Actively Recruiting
19
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States, 32610
Actively Recruiting
20
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
Actively Recruiting
21
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States, 32207
Actively Recruiting
22
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Actively Recruiting
23
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
Suspended
24
Arnold Palmer Hospital for Children
Orlando, Florida, United States, 32806
Actively Recruiting
25
Nemours Children's Hospital
Orlando, Florida, United States, 32827
Actively Recruiting
26
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
Actively Recruiting
27
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States, 33701
Actively Recruiting
28
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States, 33607
Actively Recruiting
29
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States, 30329
Actively Recruiting
30
Memorial Health University Medical Center
Savannah, Georgia, United States, 31404
Actively Recruiting
31
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States, 96826
Actively Recruiting
32
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60611
Actively Recruiting
33
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Actively Recruiting
34
OSF Children's Hospital of Illinois
Peoria, Illinois, United States, 61637
Actively Recruiting
35
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Actively Recruiting
36
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
Actively Recruiting
37
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
Actively Recruiting
38
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States, 40536
Actively Recruiting
39
Children's Hospital New Orleans
New Orleans, Louisiana, United States, 70118
Actively Recruiting
40
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States, 70121
Actively Recruiting
41
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
Actively Recruiting
42
Michigan State University
East Lansing, Michigan, United States, 48823
Suspended
43
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
Actively Recruiting
44
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Actively Recruiting
45
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Actively Recruiting
46
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Active, Not Recruiting
47
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
Actively Recruiting
48
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States, 63104
Actively Recruiting
49
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
50
Mercy Hospital Saint Louis
St Louis, Missouri, United States, 63141
Actively Recruiting
51
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
Actively Recruiting
52
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Actively Recruiting
53
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, United States, 89135
Actively Recruiting
54
Summerlin Hospital Medical Center
Las Vegas, Nevada, United States, 89144
Actively Recruiting
55
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Actively Recruiting
56
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Actively Recruiting
57
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States, 07503
Actively Recruiting
58
Albany Medical Center
Albany, New York, United States, 12208
Actively Recruiting
59
Maimonides Medical Center
Brooklyn, New York, United States, 11219
Suspended
60
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, United States, 11040
Actively Recruiting
61
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States, 10016
Actively Recruiting
62
Mount Sinai Hospital
New York, New York, United States, 10029
Actively Recruiting
63
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
Actively Recruiting
64
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
65
NYP/Weill Cornell Medical Center
New York, New York, United States, 10065
Actively Recruiting
66
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
Actively Recruiting
67
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States, 10467
Actively Recruiting
68
New York Medical College
Valhalla, New York, United States, 10595
Actively Recruiting
69
Mission Hospital
Asheville, North Carolina, United States, 28801
Actively Recruiting
70
Duke University Medical Center
Durham, North Carolina, United States, 27710
Actively Recruiting
71
East Carolina University
Greenville, North Carolina, United States, 27834
Actively Recruiting
72
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Actively Recruiting
73
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Actively Recruiting
74
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Actively Recruiting
75
Dayton Children's Hospital
Dayton, Ohio, United States, 45404
Actively Recruiting
76
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Actively Recruiting
77
Oregon Health and Science University
Portland, Oregon, United States, 97239
Actively Recruiting
78
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822
Actively Recruiting
79
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
80
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Actively Recruiting
81
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Actively Recruiting
82
Prisma Health Richland Hospital
Columbia, South Carolina, United States, 29203
Actively Recruiting
83
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States, 29605
Actively Recruiting
84
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States, 57117-5134
Actively Recruiting
85
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States, 37916
Actively Recruiting
86
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, United States, 37203
Suspended
87
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
88
Dell Children's Medical Center of Central Texas
Austin, Texas, United States, 78723
Actively Recruiting
89
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
Actively Recruiting
90
El Paso Children's Hospital
El Paso, Texas, United States, 79905
Actively Recruiting
91
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
92
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
93
Children's Hospital of San Antonio
San Antonio, Texas, United States, 78207
Actively Recruiting
94
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
Actively Recruiting
95
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Actively Recruiting
96
Scott and White Memorial Hospital
Temple, Texas, United States, 76508
Actively Recruiting
97
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
Actively Recruiting
98
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Actively Recruiting
99
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507
Actively Recruiting
100
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States, 23298
Actively Recruiting
101
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Actively Recruiting
102
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
Actively Recruiting
103
West Virginia University Charleston Division
Charleston, West Virginia, United States, 25304
Actively Recruiting
104
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Actively Recruiting
105
Sydney Children's Hospital
Randwick, New South Wales, Australia, 2031
Actively Recruiting
106
Queensland Children's Hospital
South Brisbane, Queensland, Australia, 4101
Actively Recruiting
107
Royal Children's Hospital
Parkville, Victoria, Australia, 3052
Actively Recruiting
108
Perth Children's Hospital
Perth, Western Australia, Australia, 6009
Actively Recruiting
109
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Actively Recruiting
110
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Actively Recruiting
111
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Actively Recruiting
112
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Actively Recruiting
113
Children's Hospital
London, Ontario, Canada, N6A 5W9
Actively Recruiting
114
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Actively Recruiting
115
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Actively Recruiting
116
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, Canada, J1H 5N4
Actively Recruiting
117
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, Canada, G1V 4G2
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
1
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