Recruiting PHASE2 Recurrent Langerhans Cell Histiocytosis

New treatment option for Recurrent Langerhans Cell Histiocytosis

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

ClinicalTrials.gov ID: NCT05828069

What this study is testing

What is Tovorafenib?

Tovorafenib is an investigational medicine, given as an once-weekly infusion into a vein, being studied as a potential treatment for recurrent langerhans cell histiocytosis.

Also referred to as BIIB 024, BIIB-024.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: 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).

Phase 2: a mid-size study of how well it works
Time commitment: about 1 year

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 180 to 22

You may be able to join if

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.

You likely can't join if

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...

See the full eligibility criteria

Who can 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.
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...
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...
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...
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...
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...
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...
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...
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...
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...
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
Bilirubin (sum of conjugated + unconjugated) =\ 7 days have elapsed from their most recent prior assessment)
Alanine aminotransferase (ALT) =\ 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...
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...
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...
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.

What rules you out

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...
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...
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...

The study team makes the final eligibility decision.

Where it's taking place

Birmingham, Alabama, United States
Little Rock, Arkansas, United States
Downey, California, United States
Loma Linda, California, United States
Long Beach, California, United States
Los Angeles, California, United States
Madera, California, United States
Oakland, California, United States
Orange, California, United States
Palo Alto, California, United States
San Francisco, California, United States
Aurora, Colorado, United States
Denver, Colorado, United States
Hartford, Connecticut, United States
New Haven, Connecticut, United States
Wilmington, Delaware, United States
Washington D.C., District of Columbia, United States
Fort Myers, Florida, United States
Gainesville, Florida, United States
Hollywood, Florida, United States

+ 79 more site(s).

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The study runs about 1 year per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.

Who can join this trial?

This study is enrolling all sexes, 180 days to 22 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Birmingham, Alabama, United States; Little Rock, Arkansas, United States; Downey, California, United States; Loma Linda, California, United States; Long Beach, California, United States; Los Angeles, California, United States and 93 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.