Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders

NCT02425904 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: 15-005
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 15

Brief Summary

This research study is evaluating a drug called clofarabine as a possible treatment for Langerhans Cell Histiocytosis (LCH) and and other histiocytic disorders.

Conditions

Langerhans Cell Histiocytosis

Keywords

Langerhans Cell Histiocytosis

Outcome Measures

Primary Outcomes (2)

• Response Rate (OR) of LCH Cohort

  The OR was defined as the proportion of participants achieving certain response on treatment among LCH patients, criteria were defined per protocol. Better response were defined as achieving complete disease resolution (NAD) or disease regression (AD better); intermediate response defined as stable or unchanged disease status; worse response defined as disease progression.

  Disease was evaluated at baseline and the end of cycle 2. Treatment continued after cycle 2 until disease progression or unacceptable toxicity. LCH treatment duration has a median of 5.8 months with range 2.1-7 months.

• Response Rate of LCH-related Disorders Cohort

  The OR was defined as the proportion of participants achieving certain response on treatment among LCH-related disorder patients, criteria were defined per protocol. A clinical response of progressive metabolic disease (PMD) defined as CT-based target lesion abnormal and bone marrow new or recurrent involvement; partial metabolic response (PMR) defined as CT-based target lesion decreasing or disease regressed.

  Disease was evaluated at baseline and the end of cycle 2. Treatment continued after cycle 2 until disease progression or unacceptable toxicity. Treatment duration has a median of 5.5 months with range 1.7-5.6 months.

Secondary Outcomes (3)

• 1-year Progression Free Survival (PFS)

  At 1 year

• 1-year Overall Survival (OS)

  At 1 year

• Number of Participants With at Least One Grade 3 or Higher Treatment-Related Toxicity

  Disease was evaluated at baseline and the end of cycle 2. Treatment continued after cycle 2 until disease progression or unacceptable toxicity. LCH treatment duration is median 5.8 with range 2.1-7 months; LCH-related treatment duration is 5.5 (1.7-5.6).

Study Arms (2)

Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine

EXPERIMENTAL

Participants with recurrent or refractory LCH defined as with multi-focal or multi-system disease who have recurred (or have refractory disease) after at least one prior systemic chemotherapy regimen. Patient will receive Clofarabine administered via IV on days 1-5, 25 mg/m2/day per cycle for 2 cycles. At the end of cycle 2 if no disease progression, will continue with same dose for maintenance treatment for 4 additional cycles.

Drug: Clofarabine

LCH-related disorders + Clofarabine

EXPERIMENTAL

Participants with LCH-related disorders defined as who require systemic chemotherapy including participants with Rosai Dorfman Disease (RDD) who have not responded to or recurred after treatment with corticosteroids. Erdheim Chester Disease (ECD) subjects who have confirmed presence of BRAF V600E mutation must have not responded to, have recurred after, or be unable to receive treatment with a BRAF inhibitor. Patient will receive Clofarabine administered via IV on days 1-5, 25 mg/m2/day per cycle for 2 cycles. At the end of cycle 2 if no disease progression, will continue with same dose for maintenance treatment for 4 additional cycles.

Drug: Clofarabine

Interventions

Clofarabine DRUG

second-generation purine nucleoside analog

Also known as: Clofarex, Clolar

LCH-related disorders + Clofarabine; Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior diagnosis of Langerhans Cell Histiocytosis (stratum 1) or LCH-related disorder (stratum 2) established by standard diagnostic criteria and confirmed histologically.
• Evidence of active disease (histological confirmation of reactivation or progression is not required).
• Performance Score \> 70% (use Lansky score for age \< 16 and Karnofsky score for age = \>16).
• Patients of all ages will be eligible.
• Provide signed written informed consent.
• In stratum 1, patients must have failed one prior systemic chemotherapy regimen. In stratum 2, RDD patients must have failed treatment with corticosteroid. ECD patients who have confirmed BRAF V600E mutation must have failed treatment with a BRAF inhibitor or are not considered to be eligible for such treatment.
• There is no limitation of amount or the type of prior therapy or drugs.
• Female patients of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
• Participants must have adequate marrow functions as defined below, except those with involvement of hematopoietic system for whom these criteria can be waived:
• Absolute neutrophil count ≥ 750 cells/µL
• Platelets ≥75,000/µL
• Participants must have adequate organ functions as defined below:
• Total bilirubin ≤ 2.5x institutional upper limit of normal
• AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal unless it is related to involvement by LCH

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy 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. Corticosteroid treatment is allowed.
• Participants may not be receiving any other investigational agents targeting Histiocytosis.
• Clofarabine is excreted primarily by the kidneys. Therefore, drugs with known renal toxicity (e.g.vancomycin, amphotericin B, acyclovir, cyclosporin, methotrexate, tacrolimus) should be avoided to the extent possible during the 5 days of clofarabine treatment in each cycle or, if required, administered cautiously and with close monitoring.
• Use of alternative medications (e.g., herbal or botanical that could interfere with clofarabine) is not permitted during the entire study period.
• 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 clofarabine is a nucleoside analog with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with clofarabine, breastfeeding should be discontinued if the mother is treated with clofarabine. These potential risks may also apply to other agents used in this study.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
• Patients with a history of prior hematopoietic stem cell transplantation (HSCT), elevated conjugated serum bilirubin at study entry, uncontrolled systemic fungal, bacterial, or other infection, a history of hepatitis B or C infection or a history of cirrhosis.
• Individuals who are known to be HIV-positive on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with clofarabine. In addition, these individuals 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.

Sponsors & Collaborators

• St. Baldrick's Foundation: collaborator
• Cookies for Kids' Cancer: collaborator
• North American Consortium for Histiocytosis: collaborator
• Dana-Farber Cancer Institute: lead
• Sanofi: collaborator

Study Sites (15)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Children's National Medical Center

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

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Results Point of Contact

• Title: Barbara Degar, MD
• Organization: Dana-Farber Cancer Institute/Boston Children's Hospital

Barbara_Degar@dfci.harvard.edu

617-632-5186

Study Officials

• Barbara Degar, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2015
• First Posted: April 24, 2015
• Study Start: May 1, 2015
• Primary Completion: January 1, 2020
• Study Completion (Estimated): July 30, 2026
• Last Updated: February 27, 2026
• Results First Posted: February 16, 2022

Record last verified: 2025-09

Locations

CA (1); US (14)