Cytarabine or Vinblastine Sulfate and Prednisone in Treating Participants with Langerhans Cell Histocytosis

Status: Active

Description

This phase III trial studies how well cytarabine works compared to viblastine sulfate and prednisone in treating participants with Langerhans cell histocytosis. Cytarabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinblastine sulfate and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not known if cytarabine may work better than vinblastine sulfate and prednisone in treating participants with Langerhans cell histocytosis.

Eligibility Criteria

Inclusion Criteria

  • Patient must have biopsy-confirmed diagnosis of Langerhans cell histiocytosis

Exclusion Criteria

  • Patient may not have received prior systemic chemotherapy for LCH or other malignant disorder; systemic steroids equivalent to prednisone 1 mg/kg/day cannot have been given for more than 7 days in the 30 day period prior to study enrollment; however, patients who have only received surgical or radiation therapy, intralesional injection of steroids, or topical steroids may 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 approval of the principal investigator (PI) and documentation of the rationale justifying systemic therapy
  • Patient may not have severe renal disease (creatinine greater than 3 times normal for age OR creatinine clearance < 50 ml/m^2/1.73 m^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
  • Patient may not have a Karnofsky performance score < 50% or Lansky performance score < 50%
  • Female patients may not be pregnant or breastfeeding
  • Patients of reproductive potential must use an acceptable form of birth control or abstain from sexual activity
  • Patients with human immunodeficiency virus (HIV) who are unable or unwilling to stop antiretroviral therapy for the duration of therapy may not be enrolled
  • Patients excluded for laboratory abnormalities or performance score ONLY may be enrolled on the study with the approval of the PI or designee

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Carl E. Allen
Phone: 832-826-0860
Email: ceallen@txch.org
Texas Children's Hospital
Status: Active
Contact: Carl E. Allen
Phone: 832-825-1206
Email: ceallen@txch.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine 1-year event-free survival (EFS) of patients treated with cytarabine monotherapy for Langerhans cell histiocytosis (LCH), compared directly with that of standard-of-care vinblastine sulfate (vinblastine)/prednisone in a randomized trial.

SECONDARY OBJECTIVES:

I. To evaluate durable responses with 2-year and 5-year EFS and overall survival (OS) of patients treated with cytarabine versus vinblastine/prednisone for LCH.

II. To evaluate toxicities (including psychosis, hypertension, neuropathy, fever, and headache) of patients treated with cytarabine versus vinblastine/prednisone for LCH.

III. To determine rate at which patients achieve non-active disease on cytarabine versus vinblastine/prednisone therapy.

IV. To determine whether cytarabine or vinblastine/prednisone more rapidly leads to eradication of circulating cells with BRAF-V600E or other LCH-defining mutation, and whether this prospectively correlates with disease burden.

V. To evaluate the role of fludeoxyglucose F-18 (18-FDG) positron emission tomography (PET)/computed tomography (CT) in identifying high-risk organ (liver, spleen, or bone marrow) involvement and correlating PET/CT response with presence of clinical disease activity as well as presence of circulating cells with BRAF-V600E.

VI. To utilize Response Evaluation Criteria in Solid Tumors (RECIST) criteria and terminology to assess disease response to therapy.

VII. To prospectively determine risk factors for and time to development of diabetes insipidus and neurodegenerative disease.

VIII. To store serial samples (viable white blood cells [WBCs], plasma, tumor, bone marrow, cerebrospinal fluid) for future correlative biology studies.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: INITIAL THERAPY I: Participants receive cytarabine intravenously (IV) for 5 consecutive days. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

INITIAL THERAPY II: Participants receive cytarabine as in initial therapy I.

CONTINUATION THERAPY: Participants receive cytarabine IV for 5 consecutive days. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

ARM II: INITIAL THERAPY I: Participants receive vinblastine sulfate IV once a week for 6 weeks and prednisone orally (PO) twice daily (BID) on days 1-28 in the absence of disease progression or unacceptable toxicity.

INITIAL THERAPY II: Participants with partial response (PR) or stable disease (SD) receive vinblastine sulfate as in initial therapy I and prednisone PO BID on days 1-3 of weeks 7-12.

CONTINUATION THERAPY: Beginning week 7 or 13, participants receive vinblastine sulfate IV every 3 weeks, prednisone PO BID on days 1-5 every 3 weeks and mercaptopurine PO up to week 52 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, at 18 and 24 months, then annually for 3 years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Carl E. Allen

Trial IDs

Primary ID TXCH LCH0115
Secondary IDs NCI-2018-00720
Clinicaltrials.gov ID NCT02670707