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.
o 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.)
o 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.
o 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.
Eligibility
Ages Eligible for Study: up to 18 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488605

Contacts

Contact: Histiocyte Society of America

Locations

United States, New Mexico

University of New Mexico Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Nancy Eisenberg 505-272-5980 NEisenberg@salud.unm.edu

Sponsors and Collaborators

University of New Mexico

Investigators

Principal Investigator:
Jami Frost, M.D. University of New Mexico
More Information

Study ID Numbers: H-9926-LCH III

First Received: June 14, 2007
Last Updated: June 18, 2007
ClinicalTrials.gov Identifier: NCT00488605
Health Authority: United States: Institutional Review Board

Study placed in the following topic categories:

Lymphatic Diseases Lung Diseases
Leukemia Vinblastine
Letterer-Siwe disease Langerhans cell histiocytosis
Lung Diseases, Interstitial Histiocytosis, Langerhans-Cell
Respiratory Tract Diseases Histiocytosis X
Histiocytosis

Additional relevant MeSH terms:

Neoplasms Mitosis Modulators
Neoplasms by Histologic Type Tubulin Modulators
Reticuloendotheliosis Antimitotic Agents
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic
Antineoplastic Agents Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 21, 2008