Overview

​Langerhans Cell Histiocytosis (LCH) is a disease caused by clonal proliferation of Langerhans cells and that is characterized by a spectrum of varying degrees of organ involvement and dysfunction. Treatment of LCH is risk-adapted; patients with single lesions may respond well to local treatment, whereas patients with multi-system disease and risk-organ involvement (hematopoietic, liver, spleen) require more intensive therapy. While survival for patients without organ dysfunction is excellent, mortality rates for patients with organ dysfunction may reach 30 to 40%. For patients with low-risk disease, while cure is almost universal, disease reactivations rate are in excess of 30%. Thus, new treatments are needed. Nucleoside analogues such as cladribine and cytarabine have proven to be effective in the management of LCH. More recently, clofarabine has proven to be effective in patients with cladribine and cytarabine-resistant disease, thus suggesting that this new nucleoside analogue should be investigated. In this Phase II study we are proposing to evaluate the efficacy of clofarabine in two participant populations: participants with refractory LCH with risk-organ involvement, and in low-risk participants in whom the disease has reactivated.

Primary Objectives

To estimate the response rate of participants with recurrent LCH to clofarabine within each of two strata: a) low-risk participants with disease reactivation; and, b) high-risk participants with risk-organ involvement that is refractory to standard treatment.

Secondary Objectives

1. To estimate the progression-free survival after clofarabine treatment.
2. To estimate survival of participants with refractory multi-system LCH with risk organ involvement treated with clofarabine.
3. To determine if clofarabine therapy can be delivered as planned (‘chemotherapy feasibility’), and to describe toxicities of clofarabine in participants with LCH.

Coordinating Center

Dana-Farber Cancer Institute/Boston Children’s Hospital
Department of Pediatric Oncology

​Principal Investigator

Barbara Degar, MD
Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA USA

Other Investigators

Kimo Stine, MD
Arkansas Children's Hospital, Little Rock, AR USA

Eric Jacobsen, MD
Dana-Farber Cancer Institute, Boston, MA USA

Ashish Kumar, MD, PhD
Cincinnati Children's Hospital Medical Center, Cincinnati, OH USA

Stephan Ladisch, MD
Children’s National Health System, Washington, DC USA

Rima Jubran, MD, MPH
Children's Hospital Los Angeles, Los Angeles, CA USA

Michael Hogarty, MD
The Children's Hospital of Philadelphia, Philadelphia, PA USA

David Ebb, MD
Massachusetts General Hospital, Boston, MA USA

Jean-Marie Leclerc, MD
CHU Sainte-Justine, Montreal, QC Canada

Razia Akhtar, MD
Mount Sinai Hospital Center, New York, NY USA

Michael Henry, MD
Phoenix Children's Hospital, Phoenix, AZ USA

Oussama Abla, MD
The Hospital for Sick Children, Toronto, ON Canada

Patrick Campbell, MD, PhD
St. Jude Children's Research Hospital, Memphis, TN USA

Carl Allen, MD, PhD
Texas Children’s Cancer Center/Baylor College of Medicine, Houston, TX USA

Michelle Hermiston, MD, PhD
University of California San Francisco, San Francisco, CA USA

Statistician

​Wendy London, PhD
Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA USA

Project Manager

Kerrin Tracy, MPH
Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA USA

Research Nurse

Annette Cuttle RN, BSN
​Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA USA

Patient Enrollment

If you would like information about opening the LCH-CLO at your institution, please contact Kerrin Tracy, Clinical Research Project Manager, at Kerrin_Tracy@DFCI.HARVARD.EDU.

ClinicalTrials.gov

View more information about this study on ClinicalTrials.gov.