Lenalidomide for Adult Histiocyte Disorders

A Phase II Study of Lenalidomide for Adult Histiocyte Disorders

This research study is studying a chemotherapy drug Lenalidomide as a possible treatment for one of three histiocyte disorders: Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), or histiocytic sarcoma (HS).

Study Overview

• Status: Active, not recruiting
• Conditions: Langerhans Cell Histiocytosis (LCH); Histiocytoses Erdheim-chester Disease; Histiocytic Sarcoma (HS)
• Intervention / Treatment: Drug: Lenalidomide

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved lenalidomide for your specific disease but it has been approved for other uses. Lenalidomide is a chemotherapy drug that belongs to a class of drugs called immunomodulatory drugs (IMiDs), which modify a participant's immune response in order to treat cancer. Lenalidomide alters the body's immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, it may reduce or prevent the growth of cancer cells. Lenalidomide has been shown to restore the immune cells' ability to attack and kill tumor cells Lenalidomide is approved by the FDA to treat certain cancers including multiple myeloma and myelodysplastic syndrome.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed LCH, ECD or HS. Confirmation of outside pathology at BWH will be performed but is not mandatory prior to study enrollment (see section 3).
• Detectable disease by at least one of the following modalities: CT, PET, bone scan, or MRI.

• Patients with LCH must require systemic therapy according to the Histiocyte Society LCH Evaluation and Treatment Guidelines (HS 2009)

  -- Or

• Patients with HS requiring systemic treatment as defined by disease that cannot be surgically resected and/or encompassed in a single radiation field.
• Age 18 years or older.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

• Participants must have normal organ and marrow function as defined below:

  • absolute neutrophil count ≥1,000/mcL
  • platelets ≥100,000/mcL
  • total bilirubin within 1.5 times normal institutional limits
  • AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal

  • creatinine within 2 times normal institutional limits

    --- OR

  • creatinine clearance ≥30 mL/min/1.73 m2. Note, dose adjustments are required for CrCl ≥30 mL/min but ≤60 ml/min.
• Able to take aspirin 81 mg daily as prophylactic anticoagulation if not on warfarin, low molecular weight heparin or oral factor Xa inhibitor. Patients intolerant to 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 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 because lenalidomide has known teratogenic effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide.
• Known active hepatitis B (HBV) or hepatitis C (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.
• HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lenalidomide. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide; After the screening procedures confirm participation in the research study. - Lenalidomide Oral, Daily for 21 days of each cycle	Drug: Lenalidomide; Other Names: Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Proportion of participants achieving either complete resolution of all signs or symptoms which is non-active disease (NAD) status or regression of signs or symptoms along with no new lesions which is better active-disease (AD) status per Histiocyte Society criteria any time on treatment.	Disease assessed every 3 cycles on treatment up do 12 cycles (approximately 12 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-months Progression-free Survival (PFS)	Progression-free survival (PFS) based on the Kaplan-Meier method is defined as time from registration to progression (PD) or death, censored for patients alive and progression-free at last disease assessment. PD is defined by Histiocyte criteria. Percent PFS is the percent of patients who are alive and progression-free at 12 months.	Disease assessed on treatment every 3 cycles and in long-term follow-up up to the earlier of 36 months (every 3 months for 2 years then every 6 months) or start of new anti-cancer therapy. Relevant for this endpoint was12-months estimate.
12-months Overall Survival (OS)	Overall survival (OS) based on the Kaplan-Meier method is defined as the time from registration to death, censored for patients alive at last contact. Percent OS is the percent of patients who are alive at 12 months.	12 Months
Incidence of Grade 3-4 Toxicity	Grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite (treatment-related) based on NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3) as reported on case report forms were tabulated by maximum grade. Incidence is the proportion of participants experiencing at least one treatment-related grade 3-4 AE of any type during the time of observation.	Up to 12 months on treatment.
Urine Cell Free DNA for BRAF	Quantitative serial measurements of urine cell free DNA for BRAF mutation as a biomarker of response	12 Months
Percent Change in Serum TNF-alpha Levels on Therapy From Baseline up to 12 Cycles	Serum TNF-alpha levels were quantified per established methods and maximum percent change in level from baseline derived.	Measured at baseline, day 1 of cycles 3, 6 ad 12 cycles and within 28 days post-treatment end (up to 13 months).
Plasma Cell Free DNA for BRAF	Quantitative serial measurements of plasma cell free DNA for BRAF mutation as a biomarker of response	12 months

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Celgene
• Investigators: Principal Investigator: Eric Jacobsen, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): February 1, 2024
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: August 12, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimated): August 14, 2015

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Langerhans cell histiocytosis (LCH); Erdheim-Chester disease (ECD); Histiocytic Sarcoma (HS)
• Additional Relevant MeSH Terms: Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Lymphatic Diseases; Lung Diseases, Interstitial; Histiocytic Disorders, Malignant; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Hemic and Lymphatic Diseases; Histiocytosis, Langerhans-Cell; Histiocytic Sarcoma; Erdheim-Chester Disease; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide
• Other Study ID Numbers: 15-197