Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders
NACHO-COBI
A Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib in Refractory Langerhans Cell Histiocytosis, LCH-Associated Neurodegenerative Disease, and Other Histiocytic Disorders.
1 other identifier
interventional
90
1 country
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2021
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 10, 2019
CompletedFirst Posted
Study publicly available on registry
September 6, 2019
CompletedStudy Start
First participant enrolled
April 19, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
ExpectedSeptember 18, 2025
September 1, 2025
4.6 years
August 10, 2019
September 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
12 months
Secondary Outcomes (2)
Progression Free Survival
12 months
Nature and Severity of Adverse Events
12 months
Other Outcomes (1)
Response assessment (Modified RECIST) of histiocytic lesions with specific mutations
12 months
Study Arms (4)
Patients < 21 years with recurrent LCH (Grp1)
EXPERIMENTALChildren (≥ 6 months) and young adults (\<21 years) with recurrent active LCH lesions (may also have LCH-ND).
Patients of any age with LCH-ND (Grp2)
EXPERIMENTALPatients of any age (≥ 6 months) with progressive LCH Neurodegenerative Disease (LCH-ND) without other sites of active LCH.
Patients <21 years with other histiocytic disorders (Grp3)
EXPERIMENTALNewly diagnosed or relapsed/refractory children (≥ 6 months) and young adults (\<21 years) with other histiocytic disorders including juvenile xanthogranuloma, Erdheim-Chester disease, histiocytic sarcoma and Rosai-Dorfman disease.
Patients ≥ 21 years with LCH/histiocytic disorders (Grp4)
EXPERIMENTALAdults (≥21 years) with LCH or other histiocytic disorder with recurrent active lesions (may also have LCH-ND).
Interventions
Cobimetinib 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).
Eligibility Criteria
You may qualify if:
- Age at study entry
- 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
- 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 or gastric tube.
- Biopsy proven LCH -AND
- Failure of at least front-line therapy for LCH with evaluable disease. -OR
- Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
- Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease.
- Performance Level:
- Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age.
- Adequate Hematologic Function Defined as:
- ANC ≥ 0.75 x 10\^9/L (unsupported/without growth factor stimulant)
- Platelet count ≥ 75 x 10\^9/L (unsupported/without transfusion within the past 7 days).
- +17 more criteria
You may not qualify if:
- \- Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
- 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.
- Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or \< 5 half-lives, whichever is longer, prior to study enrollment.
- Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
- For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
- Corticosteroid therapy less than or equal to 0.5 mg/kg/day averaged during the 28 days prior to study enrollment is permissible. Patients receiving corticosteroids must be on a stable or decreasing dose for 14 days prior to enrollment and discontinue once study treatment has started.
- Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
- Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
- Other active malignancy or history of secondary malignancy.
- Refractory nausea and vomiting, malabsorption, external biliary shunt
- Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
- Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Carl Allenlead
- Baylor College of Medicinecollaborator
- North American Consortium for Histiocytosiscollaborator
- Genentech, Inc.collaborator
Study Sites (12)
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Benioff Children's Hospital
San Francisco, California, 94158, United States
Children's National Hospital
Washington D.C., District of Columbia, 20010, United States
John Hopkins University School of Medicine
Baltimore, Maryland, 21287, United States
Dana Farber Cancer Institute, Boston Children's
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
NACHO Consortium
Memphis, Tennessee, 38105, United States
Children's Medical Center- UTSW
Dallas, Texas, 75235, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
University of Wisconsin-American Family Children's Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Carl E Allen, MD, PhD
Baylor College of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
August 10, 2019
First Posted
September 6, 2019
Study Start
April 19, 2021
Primary Completion
December 1, 2025
Study Completion (Estimated)
December 1, 2029
Last Updated
September 18, 2025
Record last verified: 2025-09