- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00488605
H-9926-LCH III: Treatment Protocol of the Third International Study for Langerhans Cell Histiocytosis
LCH III is an international, multicentric, prospective clinical study comprised of:
- a randomized clinical trial for multisystem "RISK" patients and
- a randomized clinical trial for multisystem "LOW RISK" patients and
- a pilot study for patients with single system MFB and localized "SPECIAL SITES"
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Therapy for "LOW RISK" Patients:
The decision as to which research program you will be assigned will be made entirely by chance. The overall time of therapy will be 6 or 12 months as randomly assigned. The research program will be with the drugs Vinblastine and Prednisone.
Initial Therapy
- Prednisone given by mouth three times a day daily as a four-week course, then gradually decreased over 2 more weeks.
- Vinblastine will be given IV (into a vein) one day a week for 6 weeks.
- Patients who have no evidence of active disease at this time will proceed to continuation therapy.
Patients whose disease response is stable, mixed or worse will receive additional therapy with:
- Prednisone in 3 divided doses by mouth for 3 days every week, from week 7-12.
Vinblastine IV one day a week for 6 more weeks.
- If the disease is gone or better after this additional therapy continuation will begin.
Continuation Therapy
- Prednisone in 3 doses daily day 1-5 every 3 weeks until the end of month 6 or 12 from start of therapy, as randomized.
- Vinblastine IV day 1 every 3 weeks until the end of month 6 or 12 from start of therapy, as randomized.
Therapy for "SPECIAL SITE" (Multi-focal Bone Involvement) Patients:
Treatment consists of an initial treatment of 6 weeks and a continuation treatment. A second course is given only to patients with progressive disease. The overall therapy time period is 6 months.
Initial Therapy 4. Prednisone given by mouth three times a day daily as a four-week course, then gradually decreased over 2 more weeks.
5. Vinblastine will be given IV (into a vein) one day a week for 6 weeks. 6. Patients who have no evidence of active disease at this time will proceed to continuation therapy.
Patients whose disease response is stable, mixed or worse will receive additional therapy with:
3. Prednisone in 3 divided doses days 1-3 weekly from week 7-12. 4. Vinblastine IV one day a week for 6 more weeks.
- If the disease is gone or better after this additional therapy continuation will begin.
Continuation Therapy 3. Prednisone in 3 doses daily day 1-5 every 3 weeks until the end of month 6. 4. Vinblastine IV day 1 every 3 weeks until the end of month 6.
Group 1 "RISK" patients:
The primary aim of the study is to compare the therapeutic efficacy of control arm A (PDN+VBL) with the experimental arm B (PDN+VBL+MTX). The primary endpoint is the proportion of non-responder in risk organs to the initial treatment.
Non-response to initial therapy is defined as:
• death within 12 weeks of initial treatment or
- progression (worse) in risk organs at week 6
- lack of response (=intermediate response or progression) in risk organs at week 12 as compared to the status of disease at week 6.
If the null hypothesis is true, the two randomized treatment arms are equally effective in terms of non-response. If the alternative hypotheses is true, there is a difference between the two randomized arms in terms of efficacy.
Group 2 "LOW RISK" patients:
The primary aim of the study is to compare the reactivation free survival rate in initial responders at week 6 with continuation treatment for 6 months (Arm LR 6) versus 12 months (Arm LR 12) in those patients without disease reactivation within the first 6 months.
If the null hypothesis is true, the reactivation rate of both randomized arms are equal. If the alternative hypothesis is true, there is a difference between the two arms in terms of reactivation frequency.
Therapy for "RISK" Patients:
Treatment A will consist of:
7. Initial Therapy 8. Prednisone given by mouth three times a day daily as a four-week course, then gradually decreased over 2 more weeks.
9. Vinblastine will be given IV (into a vein) one day a week for 6 weeks. 10. Patients who have no evidence of active disease at this time will proceed to continuation therapy.
Patients whose disease is improved or unchanged will receive additional therapy with:
5. Prednisone in 3 divided doses by mouth for 3 days every week, from week 7-12.
6. Vinblastine IV one day a week for 6 more weeks.
** If the disease is gone or better after this additional therapy continuation will begin.
Continuation Therapy:
5. 6-MP by mouth daily until the end of month 12. 6. Prednisone in 3 doses daily day 1-5 every 3 weeks until the end of month 12. 7. Vinblastine IV day 1 every 3 weeks until the end of month 12.
** Those patients whose disease didn't respond to the initial therapy by the 12th week will come off this study and proceed to other research programs.
Treatment B will consist of:
- Initial Therapy
- Prednisone given by mouth three times a day daily as a four-week course then gradually decreased over 2 more weeks.
- Vinblastine will be given IV one day a week for 6 weeks.
- Methotrexate given as a 24 hour IV infusion day 1 of weeks 1, 3, and 5, followed by leucovorin.
Leucovorin is a drug that will be given to help the body remove the methotrexate and decrease the possible side effects. (This is sometimes called a "leukovorin rescue". The drug will be given by mouth.)
- Patients who have no evidence of active disease at this time will proceed to continuation therapy.
Patients whose disease is improved or unchanged will receive additional therapy with:
- Prednisone in 3 divided doses, days 1-3 weekly from week 7-12.
- Vinblastine IV one day a week for 6 more weeks.
Methotrexate given as a 24 hour IV infusion day 1 of week 7, 9, and 11, followed by leucovorin.
- If the disease is gone or better after this additional therapy continuation will begin.
Continuation Therapy:
- 6-MP by mouth daily until the end of month 12.
- Prednisone in 3 doses daily days 1-5 every 3 weeks until the end of month 12.
- Vinblastine IV day 1 every 3 weeks until the end of month 12.
- Methotrexate by mouth once weekly until the end of month 12.
Those patients whose disease didn't respond to the initial research program by the 12th week will come off this research study and proceed to another research program.
Study Type
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
New Mexico
-
Albuquerque, New Mexico, United States, 87131
- University of New Mexico
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
All newly diagnosed patients who meet the following criteria are eligible to be enrolled and followed in the study:
- Definitive diagnosis of LCH
- Age under 18 years
- No prior treatment for LCH
Exclusion Criteria:
- Not specified
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment Arm A
|
Initial Therapy:Prednisone- by mouth 3 times/day daily as a 4-week course, then gradually decreased over 2 more weeks.
Vinblastine-IV (into a vein)1 day/week for 6 weeks.
Patients w/o evidence of active disease at this time will proceed to continuation therapy.
If disease is improved or unchanged, pts.
will receive additional therapy with: Prednisone- 3 divided doses by mouth for 3 days every week, from week 7-12.
Vinblastine- IV 1day/week for 6 more weeks.
If the disease is gone or better after this additional therapy continuation will begin.
Continuation Therapy: 6-MP:by mouth daily until the end of month 12. Prednisone in 3 doses daily day 1-5 every 3 weeks until the end of month 12. Vinblastine IV day 1 every 3 weeks until the end of month 12.
|
Experimental: Treatment Arm B
|
Initial Therapy:Prednisone-by mouth 3x/day daily as a 4-week course then gradually decreased over 2 more weeks.
Vinblastine- IV 1 day/week for 6 weeks.
Methotrexate-a 24 hour IV infusion day 1 of weeks 1, 3, and 5, followed by leucovorin.The drug will be given by mouth.
Pts w/o evidence of active disease at this time will proceed to continuation therapy.
Pts whose disease is improved or unchanged will receive additional therapy w/:Prednisone- 3 divided doses, days 1-3 weekly from week 7-12.
Vinblastine IV 1day/week for 6 more weeks.
Methotrexate-a 24 hour IV infusion day 1 of week 7, 9, and 11, followed by leucovorin.
If the disease is gone or better after this additional therapy continuation will begin.
Continuation Therapy: 6-MP by mouth daily until the end of month 12. Prednisone- 3 doses daily days 1-5 every 3 weeks until the end of month 12. Vinblastine IV day 1 every 3 weeks until the end of month 12. Methotrexate by mouth once weekly until the end of month 12.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The proportion of non-responder in risk organs to the initial treatment
Time Frame: 12 months
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 12 months
|
12 months
|
Proportion of responders (overall and in risk organs)
Time Frame: at week 6
|
at week 6
|
Proportion of responders (overall and in risk organs)
Time Frame: at week 12
|
at week 12
|
Reactivation free survival after response
Time Frame: at week 12
|
at week 12
|
Time to NAD
Time Frame: at weeks 6, 12, 7, or 13-23
|
at weeks 6, 12, 7, or 13-23
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jami Frost, M.D., University of New Mexico
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lymphatic Diseases
- Lung Diseases
- Lung Diseases, Interstitial
- Histiocytosis, Langerhans-Cell
- Histiocytosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protective Agents
- Antineoplastic Agents, Phytogenic
- Dermatologic Agents
- Micronutrients
- Vitamins
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Leucovorin
- Levoleucovorin
- Prednisone
- Methotrexate
- Vinblastine
Other Study ID Numbers
- H-9926-LCH III
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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