VEMURAFENIB for Histiocytic disorders | Langerhans cell histiocytosis | Erdheim–Chester disease | Rosai–Dorfman disease

Inclusion criteria

• {"criterion_text":"- The presence of mutations in the BRAF gene in tumor tissues and/or in ctDNA at any stage of treatment or follow-up.\n- Failure of the treatment (at least one of below needs to apply in order for this requirement to be satisfied): a. Progression on the I and/or II line treatment, including at least one risk organ; prior treatment should include a minimum of 6 weeks of weekly Vinblastine with a minimum of 28 days prednisolone or minimum 2 cycles of Cytosine Arabinoside in 4-day cycles and/or Cladribine in 5- day cycles as a 2nd line treatment, minimum 2 cycles, or other secondline treatment or b. Disease reactivation after an initial response to treatment with Vimblastine and prednisolone as the first line and/or no response to second line treatment using one of two drugs: Cytosine Arabinoside in 4- day cycles and/or Cladribine in 5-day cycles, minimum 2 cycles, or other I/ II line treatment or occurrence of involvement of at least one risk organ or c. Third or subsequent reactivation of disease with or without risk organ involvement, or d. Reactivation of disease after Vemurafenib therapy has been completed, or e. The appearance of signs of neurodegenerative disorder (ND) in MRI of the CNS.\n- Signing of informed consent for trial participation (including for Vemurafenib treatment) according with current legal regulations.\n- Consent to the use of effective contraception throughout the Vemurafenib administration period and a minimum of 1 year after discontinuation in patients at puberty and sexual maturity.\n- Participation in HISTIOGEN trial."}

Exclusion criteria

• {"criterion_text":"- Lack of inclusion criteria.\n- Pregnancy and breastfeeding .\n- Hypersensitivity to the study drug or any of its ingredients.\n- Iritis, uveitis, obstruction of the retinal veins.\n- Simultaneous treatment with other drugs which might interact with Vemurafenib.\n- Persistent toxicity related to prior therapy, making it impossible to treat with Vemurafenib.\n- Diagnosis of other malignancies before study inclusion.\n- Other acute or persistent disorders, behaviors or abnormal laboratory test results, which might increase the risk related to the participation in this clinical trial or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator's opinion, disqualify a patient from participating in the trial."}

Primary endpoints

• {"endpoint_text":"- EFS – (event-free survival).","definition_or_measurement_approach":"Event-free survival as stated (no further definition provided in the record)."}
• {"endpoint_text":"- Assessment of the safety of vemurafenib treatment by AE analysis including adverse events of a special interest.","definition_or_measurement_approach":"Safety assessed by adverse event (AE) analysis including adverse events of special interest as stated."}
• {"endpoint_text":"- Assessment of the safety of vemurafenib treatment by vital signs, laboratory tests, echocardiography and ECG findings analysis.","definition_or_measurement_approach":"Safety assessed by monitoring vital signs, laboratory tests, echocardiography and ECG findings as stated."}
• {"endpoint_text":"- To determine dose of the investigated substance in patient below 18 y.o. that provides exposition to the drug similar to exposition recommended in adults.","definition_or_measurement_approach":"Dose determination based on achieving drug exposure (pharmacokinetic/serum concentration) in patients <18 years comparable to adult exposure (PK-guided dose determination as stated)."}

Secondary endpoints

• {"endpoint_text":"- PFS (Progression-Free Survival)","definition_or_measurement_approach":"Progression-Free Survival as stated (no further definition provided)."}
• {"endpoint_text":"- OS (Overall Survival)","definition_or_measurement_approach":"Overall Survival as stated (no further definition provided)."}
• {"endpoint_text":"- ORR (Overall Response Rate)","definition_or_measurement_approach":"Overall Response Rate as stated (no further definition provided)."}
• {"endpoint_text":"- Reactivation rate after 2 years","definition_or_measurement_approach":"Rate of disease reactivation assessed at 2 years as stated."}

Poland

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

30-10-2025

Processing Time Days

458

Number Of Sites

1

Number Of Participants

25

Primary sponsor

Full Name

Instytut Matki I Dziecka

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Poland

Contract research organisations

Name

Scientia CRO Sp. z o.o.

Responsibilities

codes: 1,10,7,8,9

Third parties

• {"country":"Poland","full_name":"Uniwersytet Przyrodniczy we Wrocławiu","duties_or_roles":"tumor cells culture","organisation_type":"Educational Institution"}
• {"country":"Poland","full_name":"Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy","duties_or_roles":"NGS genetic tests","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Poland","full_name":"Sieć Badawcza Łukasiewicz – Instytut Chemii Przemysłowej im. Prof. Ignacego Mościckiego","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"Poland","full_name":"Scientia CRO Sp. z o.o.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}