H-9926-LCH III: Treatment Protocol of the Third International Study for Langerhans Cell Histiocytosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by University of New Mexico.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of New Mexico
ClinicalTrials.gov Identifier:
NCT00488605
First received: June 14, 2007
Last updated: June 23, 2010
Last verified: May 2009

June 14, 2007
June 23, 2010
February 2004
February 2010   (final data collection date for primary outcome measure)
The proportion of non-responder in risk organs to the initial treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
The proportion of non-responder in risk organs to the initial treatment [ Time Frame: 12 months ]
Complete list of historical versions of study NCT00488605 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Proportion of responders (overall and in risk organs) [ Time Frame: at week 6 ] [ Designated as safety issue: Yes ]
  • Proportion of responders (overall and in risk organs) [ Time Frame: at week 12 ] [ Designated as safety issue: Yes ]
  • Reactivation free survival after response [ Time Frame: at week 12 ] [ Designated as safety issue: Yes ]
  • Time to NAD [ Time Frame: at weeks 6, 12, 7, or 13-23 ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 12 months ]
  • Proportion of responders (overall and in risk organs) [ Time Frame: at week 6 ]
  • Proportion of responders (overall and in risk organs) [ Time Frame: at week 12 ]
  • Reactivation free survival after response [ Time Frame: at week 12 ]
  • Time to NAD
Not Provided
Not Provided
 
H-9926-LCH III: Treatment Protocol of the Third International Study for Langerhans Cell Histiocytosis
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"

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

  1. Prednisone given by mouth three times a day daily as a four-week course, then gradually decreased over 2 more weeks.
  2. Vinblastine will be given IV (into a vein) one day a week for 6 weeks.
  3. 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:

  1. Prednisone in 3 divided doses by mouth for 3 days every week, from week 7-12.
  2. 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

  1. 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.
  2. 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:

  1. Initial Therapy
  2. Prednisone given by mouth three times a day daily as a four-week course then gradually decreased over 2 more weeks.
  3. Vinblastine will be given IV one day a week for 6 weeks.
  4. Methotrexate given as a 24 hour IV infusion day 1 of weeks 1, 3, and 5, followed by leucovorin.
  5. 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:

  1. Prednisone in 3 divided doses, days 1-3 weekly from week 7-12.
  2. Vinblastine IV one day a week for 6 more weeks.
  3. 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:

  1. 6-MP by mouth daily until the end of month 12.
  2. Prednisone in 3 doses daily days 1-5 every 3 weeks until the end of month 12.
  3. Vinblastine IV day 1 every 3 weeks until the end of month 12.
  4. 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: Prednisone, Vinblastin, 6-mercaptopuroine
    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.
  • Drug: Leucovorin, Methotrexate, Vinblastine, Prednisone
    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 Name: leukovorin rescue
  • Active Comparator: Treatment Arm A
    Intervention: Drug: Prednisone, Vinblastin, 6-mercaptopuroine
  • Experimental: Treatment Arm B
    Intervention: Drug: Leucovorin, Methotrexate, Vinblastine, Prednisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
476
February 2010
February 2010   (final data collection date for primary outcome measure)

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
Both
up to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00488605
H-9926-LCH III
Yes
Jami Frost, MD; Principal Investigator, University of New Mexico - CRTC
University of New Mexico
Not Provided
Principal Investigator: Jami Frost, M.D. University of New Mexico
University of New Mexico
May 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP