Lenalidomide in Treating Patients with Histiocyte Disorders
This pilot phase II trial studies how well lenalidomide works in treating patients with Langerhans cell histiocytosis, Erdheim-Chester disease, or histiocytic sarcoma. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria
- Patients must have histologically or cytologically confirmed LCH, ECD or HS; confirmation of outside pathology at Brigham and Women’s Hospital (BWH) will be performed but is not mandatory prior to study enrollment
- Detectable disease by at least one of the following modalities: computed tomography (CT), positron emission tomography (PET), bone scan, or magnetic resonance imaging (MRI)
- Patients with LCH must require systemic therapy according to the Histiocyte Society LCH Evaluation and Treatment Guidelines OR patients with HS requiring systemic treatment as defined by disease that cannot be surgically resected and/or encompassed in a single radiation field
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within 1.5 times normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 × institutional upper limit of normal
- Creatinine within 2 times normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2; Note, dose adjustments are required for creatinine clearance (CrCl) >= 30 mL/min but =< 60 ml/min
- Able to take a minimum dose of aspirin 81 mg daily as prophylactic anticoagulation if not on warfarin, low molecular weight heparin or oral factor Xa inhibitor; patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin at doses designed to treat deep venous thrombosis
- All study participants must be registered into the mandatory Revlimid (lenalidomide) Risk Evaluation and Mitigation Strategies (REMS) program, and be willing and able to comply with the requirements of the REMS program
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
- Prior chemotherapy or radiation within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
- Participants who are receiving any other investigational agents
- Prior treatment with lenalidomide; patients previously treated with thalidomide who discontinued treatment for reasons aside from an adverse reaction to thalidomide are permitted
- History of another invasive malignancy unless treated with curative intent 5 years or more prior to study entry; patients with localized carcinoma of the cervix, non-melanoma skin cancer, or early stage prostate cancer requiring observation only are eligible regardless of timing of diagnosis
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with lenalidomide
- Known active hepatitis B (hepatitis B virus [HBV]) or hepatitis C (hepatitis C virus [HCV]) infection; patients who are positive only for HBV surface antibody as a result of prior vaccination are eligible; patients with a positive HBV core antibody but undetectable HBV viral load are eligible
- Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
- Concomitant corticosteroids unless patient has been on a stable dose of prednisone (or equivalent) of =< 10 mg daily for at least 2 weeks prior to first dose of study drug
- Inability to swallow pills
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02523040.
PRIMARY OBJECTIVES:
I. To estimate the response rate of patients with relapsed/refractory Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and histiocytic sarcoma (HS) with single agent lenalidomide.
SECONDARY OBJECTIVES:
I. To define the progression free survival (PFS) after treatment with lenalidomide.
II. To define the overall survival (OS) after treatment with lenalidomide.
III. To describe the safety profile of lenalidomide in LCH, ECD, and HS.
IV. To assess quantitative changes in urinary and plasma cell free deoxyribonucleic acid (DNA) harboring the BRAF V600E mutation and correlate the presence or absence of the BRAF V600E mutation with response.
V. To assess serial changes in tumor necrosis factor (TNF)-alpha levels in patients treated with lenalidomide.
VI. To assess the mutational landscape of these diseases using Oncopanel.
OUTLINE:
Patients receive lenalidomide orally (PO) on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 3 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorEric D. Jacobsen
- Primary ID15-197
- Secondary IDsNCI-2015-01832
- ClinicalTrials.gov IDNCT02523040