This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
For Group 2: Participant may be at least 6 months of age at the time of enrollment
For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
For Group 4: Participant must be 21 years of age or older at the time of enrollment
Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately. See below for specific consideration of prednisone and corticosteroids prior to enrollment.
Radiation therapy within the 14 days prior to enrollment.
Any prior treatment with Cobimetinib.
Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
Parallel
Cobimetinib
DrugCobimetinib will be administered at a maximal dose of 60 mg daily for patients \<18 years old and a flat dose of 40 mg daily for patients ≥18 years for 21 days on, then 7 days off, in a 28-day treatment cycle for a total of 12 cycles (approximately 12 months).
Overall Response Rates using modified RECiST criteria
Proportion of participants with (complete response, partial response, stable disease, progressive disease) by 1 year of therapy with Cobimetinib. It is assumed that at each protocol-specified timepoint, a response assessment occurs. Status calculation will occur at each timepoint for patients who have measurable disease at baseline per the criteria defined in the protocol.
Progression Free Survival
Progression Free Survival defined as the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worse.
Nature and Severity of Adverse Events
Assessment of the nature and severity of adverse events in patients treated with Cobimetinib for histiocytic disorders.
Response assessment (Modified RECIST) of histiocytic lesions with specific mutations
Response assessment using modified RECIST criteria for target lesions with specific mutations (e.g. BRAF-V600E) . Best response rate by 1 year of therapy.
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Carl Allen
Lead sponsor
Baylor College of Medicine
Sponsor institution
Baylor College of Medicine
Collaborator
North American Consortium for Histiocytosis
Collaborator
Genentech, Inc.
Collaborator
