Langerhans Cell HistiocytosisPhase 3NCT02670707
Vinblastine/Prednisone Versus Single Therapy With Cytarabine for Langerhans Cell Histiocytosis (LCH)
A Phase 3 study testing Cytarabine and Vinblastine/prednisone in people with Langerhans Cell Histiocytosis, run by Baylor College of Medicine at 11 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Langerhans Cell Histiocytosis
- What is being tested?
- Cytarabine and Vinblastine/prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 11 sitesUnited States
- Study dates
- 7 Mar 2016to Jan 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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%.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 10 recruiting
- Recruiting
Lehigh Valley Health Network- Cedar Crest
Allentown, Pennsylvania, 18103
Jacob Troutman, DO, Jacob.Troutman@lvhn.org
Annmarie Steber, (610) 402-3078, annmarie.steber@lvhn.org
- Recruiting
Dell Children's Medical Center
Austin, Texas, 78723
Virgina Harrod, MD, PhD, 512-628-1900, vlharrod@ascension.org
Rhea Robinson, 512-628-1902, rmrobinson@ascension.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Amanda Jacobson-Kelly, MD, (614) 722-3510, Amanda.Jacobson-Kelly@nationwidechildrens.org
Myra Christian-Rancy, (614) 722-3690, Myra.Christian-Rancy@nationwidechildrens.org
- Recruiting
Cook Children's Health Care System
Fort Worth, Texas, 76104
Anish Ray, MD, (682) 885-4007, Anish.Ray@cookchildrens.org
Heather Downs, (685) 885-3379, Heather.Downs@cookchildrens.org
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Olive Eckstein, MD, 832-822-4242, Eckstein@bcm.edu
- Recruiting
Vannie Cook Children's Clinic
McAllen, Texas, 78503
Juan C Bernini, MD, (956) 661-9840, jcbernin@txch.org
Jill Hartley, (832) 828-1727, jrhartl1@txch.org
- Withdrawn
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
- Recruiting
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
William Owen, MD, 757-668-7243, William.Owen@chkd.org
Sabrina Wiggington, 757-668-7909, Sabrina.Wigginton@chkd.org
- Recruiting
Stanford Children's Hospital, Lucile Packard Children's Hospital
Palo Alto, California, 94304
Michael Jeng, MD, (650) 723-5535, mjeng@stanford.edu
Stephanie Gam, (650) 724-2642, sgam@stanford.edu
- Recruiting
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Timothy Griffin, MD, 210-704-2187, Timothy.Griffin@bcm.edu
Bridget Medina, 210-704-2894, bridget.medina@christushealth.org
- Recruiting
Rady Children's Hospital - San Diego
San Diego, California, 92123
Jennifer Yu, MD, jyu@rchsd.org
Sherri Brandsen, 858-966-1700 ext. 226235, sbrandsen@rchsd.org
About this study
Official title: Randomization of Cytarabine Monotherapy Versus Standard-of-Care Vinblastine/Prednisone for Frontline Treatment of Langerhans Cell Histiocytosis (TXCH LCH0115)
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.
Read the detailed description
To be eligible to participate in this study, patients physician must have determined that they have LCH which is not treatable by surgical intervention or observation alone. If patient chooses to participate in this study, they will be assigned randomly (like flipping a coin) to one of two LCH chemotherapy treatment groups. A computer will randomly determine if they will begin to receive vinblastine/prednisone treatment or cytarabine treatment. Patient will have an equal chance (50%) to receive vinblastine/prednisone or to receive cytarabine. Neither the patient nor their doctor will be able to choose the group assignment, but the patient and their study doctor will know which treatment they are receiving.
The patient will need to have the following tests, exams, or procedures. Most of these are part of regular cancer care and may be done even if the patient does not want to join this study. Some of them may not need to be repeated if they have had them done recently. The patient's doctor will tell them which ones they need to repeat.
- History and Physical
- Blood tests
- Urine tests
- Biopsy to confirm diagnosis
- Bone Marrow biopsy/aspirate (if patient is less than 2 years old or for any patient clinical concern for bone marrow disease)*
- Lumbar puncture for spinal fluid tests (if patient has disease in pituitary gland or brain)
- The bone marrow sample procedure is as follows: The skin above the hipbone will be made numb. This area will then be sterilized and a small incision will be made. A bone marrow needle will be inserted into the hipbone and bone marrow will be withdrawn. Patient will sign a separate consent that explains this procedure in more detail.
We will also do x-rays and scans of the inside of the body. These scans may include chest and bone x-rays, ultrasound, computerized tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET). The specific tests depend on age, sites of LCH and other clinical factors. An ultrasound is a sound wave machine that uses a computer to make pictures of the tissues of the body. A CT is an x-ray machine that uses a computer to make pictures of the organs of the body. An MRI is a scan which uses a magnetic machine to make pictures of the inside of the body. A PET scan is an x-ray technique that uses a sugar solution that you drink to see activity inside the body. The PET and CT scans will look at where the LCH is in the body.
If tests show that the patient can participate in this study and they choose to participate, treatment will begin based on randomization to either the cytarabine ("experimental") arm or the vinblastine/prednisone ("standard") arm as described below.
Patient will have a history and physical and blood tests before each cycle. The cancer drugs will be given to the patient intravenously (IV). An IV is a tube placed inside a vein to give medicine to the patient. If at anytime during the study the cancer gets worse, the patient will be taken off the study treatment.
- Cytarabine ("experimental") arm Initial therapy I (Weeks 1-6)
- Cytarabine for five consecutive days. This five-day cycle will be repeated every 21 days for a total of two cycles. Patient will have scans to see how the LCH responded to the treatment during week 6. Patients who have Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at the end of Initial Therapy I, will proceed to Initial Therapy II (Weeks 7-12). Patients who have PR or SD at the end of Initial Therapy I will require reassessment again at the end of Initial Therapy II. Patients who have CR at the end of Initial Therapy I do not require disease reassessment again until Continuation Week 24. Initial therapy II (Weeks 7-12)
- Cytarabine for five consecutive days. This five-day cycle will be repeated every 21 days for a total of two cycles. Patient will have scans to see how the LCH responded to the treatment during week 12 (unless they had no active disease at week 6). If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy. If the cancer is stable and does not respond to therapy by Week 12, the patient will be taken off the study treatment. If the patient has no evidence of active disease at this time they will proceed to Continuation therapy. Continuation therapy (Weeks 13-52)
- Cytarabine for five consecutive days. This five-day cycle will be repeated every 28 days for 10 additional cycles to complete one year of therapy Patient will have scans to see how the LCH responded to the treatment at Week 24 and at the end of therapy. If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy.
- Vinblastine/prednisone ("standard") arm
Initial therapy I (Weeks 1-6)
- Prednisone given by mouth two times a day daily on days 1-28 AND
- Vinblastine will be given IV (into a vein) one day a week for 6 weeks
Patient will have scans to see how the LCH responded to the treatment after week 6. If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy. If the disease is completely gone by Week 6, patient will proceed to Continuation therapy. If the disease is only partly gone or unchanged patient will receive additional therapy with Initial therapy II.
Patient will have scans to see how the LCH responded to the treatment during Week 12 and if they had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy.
Initial therapy II (Weeks 7-12, given only if the patient does not have evidence of active disease by Week 6)
- Prednisone by mouth on the first three days of each week during weeks 7-12 AND
- Vinblastine IV weekly during weeks 7-12
If the disease is gone or better after this additional therapy Continuation therapy will begin.
Continuation therapy
- Prednisone by mouth twice daily day on days 1-5 every 3 weeks AND
- Vinblastine IV once every 3 weeks
- 6-Mercaptopurine by mouth daily NOTE: Only high risk patients will receive 6-Mercaptopurine
Patient will have scans to see how the LCH responded to the treatment at Week 24 and at the end of therapy. If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy.
STUDY FOLLOW-UP: Patient will be in this study for 5 years after completion of their therapy. The doctors will exam the patient at 1 month, 3 months, 6 months, 9 months, 12 months, then at 18 and 24 months, then yearly until 5 years after the patient is taken off treatment. At these visits the patient may have routine blood tests, scans, and the biology tests.
- Conditions
- Langerhans Cell Histiocytosis
- Being tested
- Cytarabine, Vinblastine/prednisone
- Keywords
- vinblastine, prednisone, cytarabine, Langerhans Cell Histiocytosis (LCH)
- Medical subject headings
- Histiocytosis, Langerhans-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
Also called cytosine arabinoside (ara-C)
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.
Vinblastine/prednisoneDrug
Also called Velban/Deltasone
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
| Study group | Role | What they receive |
|---|---|---|
| Cytarabine ("experimental") arm | Experimental | On this arm, patients will receive single therapy with cytarabine. Receives: Drug: Cytarabine |
| Vinblastine/prednisone ("standard") arm | Active comparator | On this arm, patients will receive standard-of-care therapy with vinblastine and prednisone. Receives: Drug: Vinblastine/prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Overall disease response at each timepoint will be assigned based on the lesion or organ system with worst response. For disease response not defined by the criteria included in the protocol, guidelines established in the RECIST criteria will be used.
Measured: 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.
Toxicity will be graded by the NCI Common Toxicity Criteria Version 5.0.
Measured: up to 60 months after completion of therapy
Rate at which patients achieve non-active disease on cytarabine versus vinblastine/prednisone therapy.
RECIST criteria will be used for assessing disease response
Measured: up to 60 months after completion of therapy
Time to eradication of BRAF-V600E cells or other LCH-defining mutation
This will be quantified by quantitative real-time PCR.
Measured: 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.
For disease response not defined by the criteria included in the protocol, guidelines established in the RECIST criteria will be used.
Measured: up to 60 months after completion of therapy
RECIST criteria and terminology in conjunction with metabolic PET imaging (where applicable) to assess disease response to therapy.
This trial will utilize RECIST criteria for assessing disease response, which uses standard oncology response criteria terminology. Using RECIST terminology, we define response criteria for organs that may not have measurable lesions (i.e. bone marrow) but are clearly critical sites of disease. In addition, definitions of response in terms of metabolic activity from PET scans will also be prospectively analyzed based on prior retrospective radiologic reviews.
Measured: up to 60 months after completion of therapy
Number of risk factors for and time to development of diabetes insipidus and neurodegenerative disease.
Evaluation of CNS+ site involvement at start of therapy, somatic BRAFV600E mutation status and measurable peripheral/marrow levels, ethnicity, age at onset, and extent of disease in predicting risk of neurodegenerative disease and/or pituitary involvement.
Measured: up to 60 months after completion of therapy
Storage of serial samples
To store serial samples (viable WBCs, plasma, tumor, bone marrow, cerebrospinal fluid) for future correlative biology studies.
Measured: up to 60 months after completion of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2016 (estimated)
- Study start7 Mar 2016
- Primary completionJan 2027 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Langerhans Cell HistiocytosisStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Olive Eckstein, Baylor College of Medicine
- Investigators
- Olive Eckstein, MD, Study chair, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02670707
- Sponsor's protocol ID
- H-37718 TXCH LCH0115
- Status last verified
- Sep 2025
- First submitted
- 4 Jan 2016
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomization of Cytarabine Monotherapy Versus Standard-of-Care Vinblastine/Prednisone for Frontline Treatment of Langerhans Cell Histiocytosis (TXCH LCH0115)
- ClinicalTrials.gov ID
- NCT02670707
- Acronym / sponsor ID
- H-37718 TXCH LCH0115
- Conditions
- Langerhans Cell Histiocytosis
- Keywords
- vinblastine, prednisone, cytarabine, Langerhans Cell Histiocytosis (LCH)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- 7 Mar 2016 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 2 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
To be eligible to participate in this study, patients physician must have determined that they have LCH which is not treatable by surgical intervention or observation alone. If patient chooses to participate in this study, they will be assigned randomly (like flipping a coin) to one of two LCH chemotherapy treatment groups. A computer will randomly determine if they will begin to receive vinblastine/prednisone treatment or cytarabine treatment. Patient will have an equal chance (50%) to receive vinblastine/prednisone or to receive cytarabine. Neither the patient nor their doctor will be able to choose the group assignment, but the patient and their study doctor will know which treatment they are receiving.
The patient will need to have the following tests, exams, or procedures. Most of these are part of regular cancer care and may be done even if the patient does not want to join this study. Some of them may not need to be repeated if they have had them done recently. The patient's doctor will tell them which ones they need to repeat.
- History and Physical
- Blood tests
- Urine tests
- Biopsy to confirm diagnosis
- Bone Marrow biopsy/aspirate (if patient is less than 2 years old or for any patient clinical concern for bone marrow disease)*
- Lumbar puncture for spinal fluid tests (if patient has disease in pituitary gland or brain)
- The bone marrow sample procedure is as follows: The skin above the hipbone will be made numb. This area will then be sterilized and a small incision will be made. A bone marrow needle will be inserted into the hipbone and bone marrow will be withdrawn. Patient will sign a separate consent that explains this procedure in more detail.
We will also do x-rays and scans of the inside of the body. These scans may include chest and bone x-rays, ultrasound, computerized tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET). The specific tests depend on age, sites of LCH and other clinical factors. An ultrasound is a sound wave machine that uses a computer to make pictures of the tissues of the body. A CT is an x-ray machine that uses a computer to make pictures of the organs of the body. An MRI is a scan which uses a magnetic machine to make pictures of the inside of the body. A PET scan is an x-ray technique that uses a sugar solution that you drink to see activity inside the body. The PET and CT scans will look at where the LCH is in the body.
If tests show that the patient can participate in this study and they choose to participate, treatment will begin based on randomization to either the cytarabine ("experimental") arm or the vinblastine/prednisone ("standard") arm as described below.
Patient will have a history and physical and blood tests before each cycle. The cancer drugs will be given to the patient intravenously (IV). An IV is a tube placed inside a vein to give medicine to the patient. If at anytime during the study the cancer gets worse, the patient will be taken off the study treatment.
- Cytarabine ("experimental") arm Initial therapy I (Weeks 1-6)
- Cytarabine for five consecutive days. This five-day cycle will be repeated every 21 days for a total of two cycles. Patient will have scans to see how the LCH responded to the treatment during week 6. Patients who have Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at the end of Initial Therapy I, will proceed to Initial Therapy II (Weeks 7-12). Patients who have PR or SD at the end of Initial Therapy I will require reassessment again at the end of Initial Therapy II. Patients who have CR at the end of Initial Therapy I do not require disease reassessment again until Continuation Week 24. Initial therapy II (Weeks 7-12)
- Cytarabine for five consecutive days. This five-day cycle will be repeated every 21 days for a total of two cycles. Patient will have scans to see how the LCH responded to the treatment during week 12 (unless they had no active disease at week 6). If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy. If the cancer is stable and does not respond to therapy by Week 12, the patient will be taken off the study treatment. If the patient has no evidence of active disease at this time they will proceed to Continuation therapy. Continuation therapy (Weeks 13-52)
- Cytarabine for five consecutive days. This five-day cycle will be repeated every 28 days for 10 additional cycles to complete one year of therapy Patient will have scans to see how the LCH responded to the treatment at Week 24 and at the end of therapy. If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy.
- Vinblastine/prednisone ("standard") arm
Initial therapy I (Weeks 1-6)
- Prednisone given by mouth two times a day daily on days 1-28 AND
- Vinblastine will be given IV (into a vein) one day a week for 6 weeks
Patient will have scans to see how the LCH responded to the treatment after week 6. If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy. If the disease is completely gone by Week 6, patient will proceed to Continuation therapy. If the disease is only partly gone or unchanged patient will receive additional therapy with Initial therapy II.
Patient will have scans to see how the LCH responded to the treatment during Week 12 and if they had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy.
Initial therapy II (Weeks 7-12, given only if the patient does not have evidence of active disease by Week 6)
- Prednisone by mouth on the first three days of each week during weeks 7-12 AND
- Vinblastine IV weekly during weeks 7-12
If the disease is gone or better after this additional therapy Continuation therapy will begin.
Continuation therapy
- Prednisone by mouth twice daily day on days 1-5 every 3 weeks AND
- Vinblastine IV once every 3 weeks
- 6-Mercaptopurine by mouth daily NOTE: Only high risk patients will receive 6-Mercaptopurine
Patient will have scans to see how the LCH responded to the treatment at Week 24 and at the end of therapy. If the patient had LCH in their bone marrow (BM) at the beginning of the study, they will have another BM biopsy.
STUDY FOLLOW-UP: Patient will be in this study for 5 years after completion of their therapy. The doctors will exam the patient at 1 month, 3 months, 6 months, 9 months, 12 months, then at 18 and 24 months, then yearly until 5 years after the patient is taken off treatment. At these visits the patient may have routine blood tests, scans, and the biology tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cytarabine ("experimental") arm | Experimental | Drug: CytarabineOn this arm, patients will receive single therapy with cytarabine. |
| Vinblastine/prednisone ("standard") arm | Active comparator | Drug: Vinblastine/prednisoneOn this arm, patients will receive standard-of-care therapy with vinblastine and prednisone. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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%.
Key exclusion criteria (12 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytarabineAlso: cytosine arabinoside (ara-C)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. | Drug | Cytarabine ("experimental") arm |
| Vinblastine/prednisoneAlso: Velban/DeltasoneVinblastine/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 | Drug | Vinblastine/prednisone ("standard") arm |
Primary outcome
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).
Time frame: up to 60 months
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).
8 secondary outcomes
Durable responses with 2-year and 5-year EFS and OS of the patients treated with cytarabine versus vinblastine/prednisone for LCH.
Time frame: 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.
Time frame: up to 60 months after completion of therapy
Rate at which patients achieve non-active disease on cytarabine versus vinblastine/prednisone therapy.
Time frame: up to 60 months after completion of therapy
Time to eradication of BRAF-V600E cells or other LCH-defining mutation
Time frame: 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.
Time frame: up to 60 months after completion of therapy
RECIST criteria and terminology in conjunction with metabolic PET imaging (where applicable) to assess disease response to therapy.
Time frame: up to 60 months after completion of therapy
Number of risk factors for and time to development of diabetes insipidus and neurodegenerative disease.
Time frame: up to 60 months after completion of therapy
Storage of serial samples
Time frame: up to 60 months after completion of therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Olive Eckstein, MD study chair
Baylor College of Medicine
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cytarabine and Vinblastine/prednisone in people with Langerhans Cell Histiocytosis, run by Baylor College of Medicine at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olive Eckstein, MD (832-822-4242, Eckstein@bcm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.