To check the safety, efficacy and tolerability of the drug vemurafenib, and to determine the duration of treatment in children with BRAF mutationresistant histiocytic cell hyperplasia resistant to conventional therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Matki I Dziecka

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 May 2021 → ongoing

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-515805-25-00

EudraCT number

2020-005052-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy, Safety

Optimalization of the time and dosage of Vemurafenib in BRAF positive juvenile patients with refractory histiocytosis.

Secondary objectives 3

1. To evaluate the safety of Vemurafenib treatment in BRAF positive juvenile patients with refractory histiocytosis.
2. To evaluate the clinical response to Vemurafenib treatment in relation to pharmacokinetics/serum drug concentration.
3. To evaluate organ toxicity of Vemurafenib treatment in relation to pharmacokinetics/serum drug concentration.

Conditions and MedDRA coding

histiocytic cell proliferation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. The presence of mutations in the BRAF gene in tumor tissues and/or in ctDNA at any stage of treatment or follow-up.
2. 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.
3. Signing of informed consent for trial participation (including for Vemurafenib treatment) according with current legal regulations.
4. 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.
5. Participation in HISTIOGEN trial.

Exclusion criteria 8

1. Lack of inclusion criteria.
2. Pregnancy and breastfeeding .
3. Hypersensitivity to the study drug or any of its ingredients.
4. Iritis, uveitis, obstruction of the retinal veins.
5. Simultaneous treatment with other drugs which might interact with Vemurafenib.
6. Persistent toxicity related to prior therapy, making it impossible to treat with Vemurafenib.
7. Diagnosis of other malignancies before study inclusion.
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. EFS – (event-free survival).
2. Assessment of the safety of vemurafenib treatment by AE analysis including adverse events of a special interest.
3. Assessment of the safety of vemurafenib treatment by vital signs, laboratory tests, echocardiography and ECG findings analysis.
4. 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.

Secondary endpoints 4

1. PFS (Progression-Free Survival)
2. OS (Overall Survival)
3. ORR (Overall Response Rate)
4. Reactivation rate after 2 years

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Matki I Dziecka

Sponsor organisation

Instytut Matki I Dziecka

Address

Ul Marcina Kasprzaka 17 A

City

Warsaw

Postcode

01-211

Country

Poland

Scientific contact point

Organisation

Instytut Matki I Dziecka

Contact name

Klinika Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID

Public contact point

Organisation

Instytut Matki I Dziecka

Contact name

Klinika Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications