Vinblastine/Prednisone Versus Single Therapy With Cytarabine for Langerhans Cell Histiocytosis (LCH)
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|ClinicalTrials.gov Identifier: NCT02670707|
Recruitment Status : Recruiting
First Posted : February 2, 2016
Last Update Posted : June 4, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Langerhans Cell Histiocytosis||Drug: Cytarabine Drug: Vinblastine/prednisone||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||124 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomization of Cytarabine Monotherapy Versus Standard-of-Care Vinblastine/Prednisone for Frontline Treatment of Langerhans Cell Histiocytosis (TXCH LCH0115)|
|Actual Study Start Date :||March 7, 2016|
|Estimated Primary Completion Date :||January 2023|
|Estimated Study Completion Date :||January 2027|
Experimental: Cytarabine ("experimental") arm
On this arm, patients will receive single therapy with 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.
Other Name: cytosine arabinoside (ara-C)
Active Comparator: Vinblastine/prednisone ("standard") arm
On this arm, patients will receive standard-of-care therapy with vinblastine and 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
Other Name: Velban/Deltasone
- 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).
- 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 ]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.
- 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 ]Toxicity will be graded by the NCI Common Toxicity Criteria Version 5.0.
- Rate at which patients achieve non-active disease on cytarabine versus vinblastine/prednisone therapy. [ Time Frame: up to 60 months after completion of therapy ]RECIST criteria will be used for assessing disease response
- Time to eradication of BRAF-V600E cells or other LCH-defining mutation [ Time Frame: within 6-24 weeks of therapy initiation ]This will be quantified by quantitative real-time PCR.
- 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 ]For disease response not defined by the criteria included in the protocol, guidelines established in the RECIST criteria will be used.
- 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 ]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.
- 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 ]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.
- Storage of serial samples [ Time Frame: up to 60 months after completion of therapy ]To store serial samples (viable WBCs, plasma, tumor, bone marrow, cerebrospinal fluid) for future correlative biology studies.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02670707
|Contact: Olive Eckstein, MD||832-822-4242||Eckstein@bcm.edu|
|Contact: Carl E. Allen, MD, PhDemail@example.com|
|United States, California|
|Rady Children's Hospital - San Diego||Recruiting|
|San Diego, California, United States, 92123|
|Contact: Jennifer Yu, MD firstname.lastname@example.org|
|Contact: Sherri Brandsen 858-966-1700 ext 226235 email@example.com|
|Principal Investigator: Jennifer Yu, MD|
|United States, Texas|
|Dell Children's Medical Center||Recruiting|
|Austin, Texas, United States, 78723|
|Contact: Virgina Harrod, MD, PhD 512-628-1900 firstname.lastname@example.org|
|Contact: Rhea Robinson 512-628-1902 email@example.com|
|Principal Investigator: Virgina Harrod, MD, PhD|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Olive Eckstein, MD 832-822-4242 Eckstein@bcm.edu|
|Children's Hospital of San Antonio||Recruiting|
|San Antonio, Texas, United States, 78207|
|Contact: Timothy Griffin, MD 210-704-2187 Timothy.Griffin@bcm.edu|
|Contact: Bridget Medina 210-704-2894 firstname.lastname@example.org|
|Principal Investigator: Timothy Griffin, MD|
|United States, Virginia|
|Children's Hospital of The King's Daughters||Recruiting|
|Norfolk, Virginia, United States, 23507|
|Contact: William Owen, MD 757-668-7243 William.Owen@chkd.org|
|Contact: Sabrina Wiggington 757-668-7909 Sabrina.Wigginton@chkd.org|
|Principal Investigator: William Owen, MD|
|Study Chair:||Olive Eckstein, MD||Baylor College of Medicine|