Vinblastine/Prednisone Versus Single Therapy With Cytarabine for Langerhans Cell Histiocytosis (LCH)

NCT02670707 | Recruiting Phase 3 DMC

• 1 other identifier: H-37718 TXCH LCH0115
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 11

Brief Summary

Langerhans Cell Histiocytosis (LCH) is a type of cancer that can damage tissue or cause lesions to form in one or more places in the body. Langerhans cell histiocytosis (LCH) is a cancer that begins in LCH cells (a type of dendritic cell which fights infection). Sometimes there are mutations (changes) in LCH cells as they form. These include mutations of the BRAF gene. These changes may make the LCH cells grow and multiply quickly. This causes LCH cells to build up in certain parts of the body, where they can damage tissue or form lesions. For most patients with LCH, standard-of-care vinblastine/prednisone are used as front-line therapy while cytarabine therapy has been used as therapy for patients who develop recurrence. No alternate treatment strategy has been developed for frontline therapy in LCH. The purpose of this research study is to compare previously used vinblastine/prednisone to single therapy with cytarabine for LCH. We will evaluate the utility of an imaging study called a positron emission tomography (PET) scan to more accurately assess areas of LCH involvement not otherwise seen in other imaging studies as well as response to therapy. We also want to identify if genetic and other biomarkers (special proteins in patient's blood and in patient's cancer) relate to the response of patients LCH to study treatment.

Conditions

Langerhans Cell Histiocytosis

Keywords

vinblastine; prednisone; cytarabine; Langerhans Cell Histiocytosis (LCH)

Outcome Measures

Primary Outcomes (1)

• Time to determine 1-year event-free survival (EFS) of patients treated with cytarabine monotherapy for LCH, compared directly with that of standard-of-care vinblastine/prednisone (Events include progression of LCH, relapse, or death).

  A Kaplan-Meier curve will be used to compare event-free survival between treatment groups. Curves will be compared using the log-rank statistic. Patients will be followed for up to 5 years after one year of therapy. Patients who have not had the event by the 5-year mark will be censored observations. Patients who are lost to follow-up without having an event will be censored at the time of last contact. Statistical significance will be assessed at the 0.05 level. A Cox proportional hazards model will also be used to estimate the Hazards Rate for combined events in the Cytarabine group versus standard therapy. A multiple regression model will also be used to estimate the adjusted HRs for genotype and baseline risk of death (high vs. low).

  up to 60 months

Secondary Outcomes (8)

• Durable responses with 2-year and 5-year EFS and OS of the patients treated with cytarabine versus vinblastine/prednisone for LCH.

  2-years and 5-years post treatment

• Number of toxicities (including psychosis, hypertension, neuropathy, fever, headache) in the patients treated with cytarabine versus vinblastine/prednisone for LCH.

  up to 60 months after completion of therapy

• Rate at which patients achieve non-active disease on cytarabine versus vinblastine/prednisone therapy.

  up to 60 months after completion of therapy

• Time to eradication of BRAF-V600E cells or other LCH-defining mutation

  within 6-24 weeks of therapy initiation

• Number of patients who have 18-FDG PET/CT positivity in identifying high-risk organ (liver, spleen, or bone marrow) involvement and correlation of PET/CT response with presence of disease activity as well as presence of circulating cells with BRAF-V600E.

  up to 60 months after completion of therapy

Study Arms (2)

Cytarabine ("experimental") arm

EXPERIMENTAL

On this arm, patients will receive single therapy with cytarabine.

Drug: Cytarabine

Vinblastine/prednisone ("standard") arm

ACTIVE COMPARATOR

On this arm, patients will receive standard-of-care therapy with vinblastine and prednisone.

Drug: Vinblastine/prednisone

Interventions

Cytarabine DRUG

Cytarabine 100 mg/m\^2/day IV for five consecutive days. This five-day cycle will be repeated every 21 days for a total of four cycles for all patients regardless of response. Each new cycle may not begin until absolute neutrophil count (ANC) is ≥ 750/mcL and platelet count is ≥ 75,000/mcL.

Also known as: cytosine arabinoside (ara-C)

Cytarabine ("experimental") arm

Vinblastine/prednisone DRUG

Vinblastine/Prednisone +/- 6-mercaptopurine based on risk category. Patients with high-risk organ involvement (liver, spleen, hematopoeitic system) will receive 6-mercaptopurine during Continuation Therapy as this is the current standard of care treatment. Vinblastine 6 mg/m\^2/dose IV push weekly for patients ≥ 12 months of age. Vinblastine will be dosed at 3 mg/m\^2/dose for patients under 6 months of age, and dosed at 4.5 mg/m\^2/dose for patients 6 months of age to 11.99 months of age. Prednisone (or prednisolone) 20 mg/m2/dose by mouth twice a day

Also known as: Velban/Deltasone

Vinblastine/prednisone ("standard") arm

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient must have biopsy-confirmed diagnosis of Langerhans cell histiocytosis.
• Patient must be between 0-21 years of age.
• Patient must have a Karnofsky performance score ≥ 50% or Lansky performance score ≥ 50%.

You may not qualify if:

• Patient may not have received any prior systemic cytotoxic or other chemotherapies for LCH or any other malignant disorder prior to the initiation of protocol therapy on TXCH LCH0115 with the exception of:
• Steroid pretreatment: Systemic glucocorticosteroids (prednisone, methylprednisone, dexamethasone, etc.) for less than or equal to 120 hours (5 days) in the 7 days prior to initiating protocol therapy or for less than or equal to 336 hours (14 days) in the 28 days before the initiation of protocol therapy does not affect eligibility. The dose of steroid previously given does not affect eligibility. Patients who have only received surgical or radiation therapy, intralesional injection of steroids, inhalational steroids, systemic mineralocorticoids (hydrocortisone), or topical steroids may also be enrolled.
• Patient may not have disease limited to a single skin or bone site, with the following exceptions:
• Central Nervous System (CNS) risk lesions/special site disease: patients with single bone sites that are CNS-risk (sphenoid, mastoid, orbital, zygomatic, ethmoid, maxillary, or temporal bones, the cranial fossa, pituitary gland or neurodegenerative disease) or are "special sites" (odontoid peg, vertebral lesion with intraspinal soft tissue extension) require systemic therapy as standard of care and thus are eligible for the study.
• Functionally critical lesions: A single lesion not described above which may cause "functionally critical anatomic abnormality" wherein attempts at local therapy (such as surgical curettage or radiation) would cause unacceptable morbidity. These patients may be enrolled with written approval of the Coordinating Center PI or Vice-Chair and documentation of the rationale justifying systemic therapy.
• Asynchronous multisite LCH presentation: A patient may also have any single site of disease involvement at the time of enrollment if they previously had at least one other site of LCH disease in the past (which may have been treated with local therapy/surgery as described), as long as no systemic therapy was previously given per protocol guidelines.
• Patient may not have severe renal disease (creatinine greater than 3 times normal for age OR creatinine clearance \< 50 ml/m2/1.73m\^2).
• Patient may not have severe hepatic disease (direct bilirubin greater than 3 mg/dl OR aspartate aminotransferase (AST) greater than 500 IU/L), unless hepatic injury is due to LCH.
• Female patients may not be pregnant or breastfeeding.
• Patients of reproductive potential not willing to use an adequate method of birth control for the duration of the study.
• Patients who are HIV positive may not be enrolled.
• NOTE: Patients excluded for laboratory abnormalities or performance score only may be enrolled on the study with written approval from the Coordinating Center PI or Vice-Chair.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (11)

Stanford Children's Hospital, Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

RECRUITING

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

WITHDRAWN

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Lehigh Valley Health Network- Cedar Crest

Allentown, Pennsylvania, 18103, United States

RECRUITING

Dell Children's Medical Center

Austin, Texas, 78723, United States

RECRUITING

Cook Children's Health Care System

Fort Worth, Texas, 76104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Vannie Cook Children's Clinic

McAllen, Texas, 78503, United States

RECRUITING

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

RECRUITING

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

RECRUITING

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Interventions

Cytarabine; Vinblastine; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Olive Eckstein, MD

  Baylor College of Medicine

  STUDY CHAIR

Central Study Contacts

Olive Eckstein, MD

CONTACT

832-822-4242; Eckstein@bcm.edu

Carl E. Allen, MD, PhD

CONTACT

832-826-0860; ceallen@txch.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: February 2, 2016
• Study Start: March 7, 2016
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)