Actively Recruiting

Phase 2
All Genders
NCT04079179

Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders

Led by Carl Allen · Updated on 2025-09-18

90

Participants Needed

12

Research Sites

449 weeks

Total Duration

On this page

Sponsors

C

Carl Allen

Lead Sponsor

B

Baylor College of Medicine

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders

Who Can Participate

All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • For Group 1: At least 6 months and less than 21 years old at enrollment
  • For Group 2: At least 6 months old at enrollment
  • For Group 3: At least 6 months and less than 21 years old at enrollment
  • For Group 4: 21 years or older at enrollment
  • Able to take medication by mouth or enteral route (oral suspension, tablet, nasogastric or gastric tube)
  • Biopsy-proven Langerhans cell histiocytosis (LCH) with failure of at least front-line therapy and evaluable disease, or diagnosis of LCH-associated neurodegenerative disease with recent progression, or biopsy-proven juvenile xanthogranuloma (JXG), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), histiocytic sarcoma, or other histiocytic lesions with active disease
  • Karnofsky performance score ≥ 50% for patients >16 years and Lansky score ≥ 50% for patients ≤16 years
  • Adequate blood counts: ANC ≥ 0.75 x 10^9/L without growth factors, platelet count ≥ 75 x 10^9/L without transfusion in past 7 days (or with transfusion support if marrow disease), hemoglobin ≥ 8 g/dL without transfusion in past 7 days (or with transfusion support if marrow disease)
  • Adequate kidney function by creatinine clearance or serum creatinine limits by age and gender
  • Adequate liver function: bilirubin ≤1.5 x ULN, AST and ALT ≤ 3x ULN (or ≤ 5x ULN if liver involved), serum albumin ≥ 2 g/dL
  • For liver disease caused by histiocytic disorder, may enroll with abnormal liver tests if documented
  • Adequate heart function with fractional shortening ≥ 30% or ejection fraction ≥ 50% by echocardiogram or MUGA within 28 days prior to enrollment
  • Female patients of childbearing potential must have negative pregnancy test and agree to contraceptive measures; males with partners of childbearing potential must agree to contraception during treatment and for 3 months after
Not Eligible

You will not qualify if you...

  • Use of strong CYP3A4 inducers or inhibitors within 14 days prior to enrollment, including certain antibiotics, antifungals, grapefruit juice, or St. John's wort
  • Prior chemotherapy, immunotherapy, radiotherapy, or targeted therapy within specified timeframes prior to enrollment (e.g., radiation within 14 days, investigational therapy within 4 weeks, stem cell transplant within 90 days)
  • Prior treatment with cobimetinib
  • Recent use of hematopoietic growth factors within 7-14 days before enrollment
  • Use of hormonal therapy (except hormone replacement or oral contraceptives), immunotherapy, biologics, investigational or herbal cancer therapy within 28 days or less than 5 half-lives prior to enrollment
  • Use of anticoagulants within 7 days prior to enrollment for patients with brain tumors
  • Corticosteroid therapy above 0.5 mg/kg/day or unstable dosing
  • Taking anticoagulants or having bleeding disorders unrelated to histiocytic disease
  • Other active cancers or history of secondary malignancy
  • Severe nausea, vomiting, malabsorption, biliary shunt
  • Active infections within 28 days prior to enrollment
  • Recent major surgery or traumatic injury within 28 days
  • History of significant bowel resection or malabsorption
  • History of pneumonitis
  • Significant eye conditions or risk factors for retinal vein occlusion
  • Prior solid organ transplantation
  • Any disease or condition deemed unsafe by the investigator
  • Significant cardiac problems including unstable arrhythmias, angina, heart failure, recent heart attack
  • Known chronic HIV infection
  • Recent or significant CNS hemorrhage
  • Pregnant or breastfeeding women

AI-Screening

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Trial Site Locations

Total: 12 locations

1

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85016

Actively Recruiting

2

Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202

Actively Recruiting

3

Children's Hospital of Orange County

Orange, California, United States, 92868

Actively Recruiting

4

UCSF Benioff Children's Hospital

San Francisco, California, United States, 94158

Actively Recruiting

5

Children's National Hospital

Washington D.C., District of Columbia, United States, 20010

Actively Recruiting

6

John Hopkins University School of Medicine

Baltimore, Maryland, United States, 21287

Actively Recruiting

7

Dana Farber Cancer Institute, Boston Children's

Boston, Massachusetts, United States, 02215

Actively Recruiting

8

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Actively Recruiting

9

NACHO Consortium

Memphis, Tennessee, United States, 38105

Not Yet Recruiting

10

Children's Medical Center- UTSW

Dallas, Texas, United States, 75235

Actively Recruiting

11

Texas Children's Hospital

Houston, Texas, United States, 77030

Actively Recruiting

12

University of Wisconsin-American Family Children's Hospital

Madison, Wisconsin, United States, 53792

Terminated

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Research Team

C

Carl E Allen, MD, PhD

CONTACT

O

Olive Eckstein, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

4

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