Cytarabine or Vinblastine Sulfate and Prednisone in Treating Patients with Langerhans Cell Histocytosis
This phase III trial studies how well cytarabine works compared to vinblastine sulfate and prednisone in treating patients 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 patients with Langerhans cell histocytosis.
Inclusion Criteria
- 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%
Exclusion Criteria
- 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 =< 120 hours (5 days) in the 7 days prior to initiating protocol therapy or for =< 336 hours (14 days) in the 28 days prior to initiating protocol therapy. Prior exposure to ANY steroids that occurred > 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 be 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 principal investigator (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/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
- 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 human immunodeficiency virus (HIV) positive may not be enrolled
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT02670707.
Locations matching your search criteria
United States
California
Palo Alto
San Diego
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Columbus
Texas
Austin
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PRIMARY OBJECTIVE:
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: Patients are randomized to 1 of 2 arms.
ARM I: INITIAL THERAPY I: Patients receive cytarabine intravenously (IV) for 5 consecutive days. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
INITIAL THERAPY II: Patients receive cytarabine as in initial therapy I.
CONTINUATION THERAPY: Patients receive cytarabine IV for 5 consecutive days. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: INITIAL THERAPY I: Patients 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: Patients 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, patients 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 PhasePhase III
Trial Typetreatment
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorOlive Simone Eckstein
- Primary IDTXCH LCH0115
- Secondary IDsNCI-2018-00720, H-37718
- ClinicalTrials.gov IDNCT02670707