NCT02670707

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

Randomization of Cytarabine Monotherapy Versus Standard-of-Care Vinblastine/Prednisone for Frontline Treatment of Langerhans Cell Histiocytosis (TXCH LCH0115)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 124 (estimated)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

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. 1. 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. 2. 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

Interventions

Type	Name	Description
DRUG	Cytarabine	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	Vinblastine/prednisone	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

Timeline

• Start date: 2016-03-07
• Primary completion: 2027-01-01
• Completion: 2029-01-01
• First posted: 2016-02-02
• Last updated: 2025-09-11

Locations

11 sites across 1 country: United States