Triptorelin for Ovary Protection in Childhood Onset Lupus

Condition(s) targeted: Systemic Lupus Erythematosus

Intervention: Triptorelin pamoate (Trelstar Depot) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: FDA Office of Orphan Products Development

Official(s) and/or principal investigator(s):
Hermine I Brunner, M.D. M.Sc., Principal Investigator, Affiliation: Children's Hospital Medical Center, Cincinnati

Overall contact:
Hermine I Brunner, M.D. M.Sc., Phone: 513-636-7275, Email: hermine.brunner@cchmc.org

The purpose of this study is to test the safety of triptorelin when used for the protection of the ovaries (pair of female reproductive organs) during cyclophosphamide therapy for systemic lupus erythematosus (SLE; lupus) and to see what effects (good or bad) it has on patients. The study will be done with female patients who have been diagnosed with systemic lupus erythematosus, are younger than 21 years of age, and require intravenous cyclophosphamide to control the disease. Each patient will be in the study for approximately 23 months, until 4 months after the intravenous cyclophosphamide treatment has been completed.

This study is being conducted at 7 sites across the United States (New York, Chicago, Milwaukee, Columbus, Seattle, Los Angeles, Cincinnati). A total of 50 patients will participate in this study.

Each patient will be randomized (assigned) to one of 5 groups. Randomization means that patients are put into a group completely by chance. It is like flipping a coin. Neither the patient nor the study staff knows what group the patient is in. The patient has a 20% chance of being placed in any group.

Study design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Diagnostic

Primary outcome: To determine the dose of triptorelin that will maintain complete ovarian suppression between monthly injections

Secondary outcome: To optimize the time interval at triptorelin injection and infusion of cyclophosphamide

Detailed description: Lupus is an autoimmune disease that may harm all organs in the body and especially affects the kidney, brain, skin and lungs. Cyclophosphamide is a very effective medication to treat lupus, but it can damage the ovaries (pair of reproductive organs).

Only female lupus patients may participate in this study.

Minimum age: 9 Years. Maximum age: 21 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Females under the age of 21 and non-pregnant

- Tanner stage of 2 or above as determined by physical examination of breast stage

- Diagnosis with SLE using the updated American College of Rheumatology (ACR)

Classification Criteria for SLE 1

- Severe SLE requiring cyclophosphamide therapy

- Bone mineral density z-score > - 2. 0

- Must be using a medically acceptable form of birth control during the study and must

not be pregnant at the screening visit

- No clinically significant abnormal findings other than those consistent with the

diagnosis of childhood-onset SLE (cSLE) on the physical examination, medical history or clinical laboratory results during screening

- Currently on any combination of medication but must not have been treated with more

than one dose of cyclophosphamide or other gonadotoxic medications in the past

- Voluntary consent or, if under the age of consent, assent to participate in this

study with permission by a legal guardian

Exclusion Criteria:

- Male patients of any age

- Female patients with a Tanner stage of 1

- Positive blood pregnancy test at screening or taking oral or injectable birth-control

medications

- Prior exposure to more than one dose of gonadotoxic medications including

cyclophosphamide

- History of allergic or adverse response to triptorelin

- Diagnosed with hypogonadism prior to cyclophosphamide exposure

- Acutely life-threatening disease activity that prohibits inclusion in a clinical

trial

- History of clinically significant gastrointestinal tract, renal, hepatic, endocrine,

oncologic, pulmonary (asthma accepted), or cardiovascular disease; or a history of tuberculosis, epilepsy, diabetes, depression, psychosis, or any other non-cSLE condition, which in the opinion of the physician, would jeopardize the safety of the subject or impact the validity of the study results

- Patient age 18 years of younger with severe depression as defined by a CDI

(Children's Depression Inventory) score of > 23 or a patient age 19 to 21 years with severe depression as defined by a BDI (Beck's Depression Inventory) score > 29

- Patient admits to suicidal thoughts at screening visit

- Bone mineral density lower than z = -2. 0.

Hermine I Brunner, M.D. M.Sc., Phone: 513-636-7275, Email: hermine.brunner@cchmc.org

Children's Hospital of Los Angeles, Los Angeles, California 90027, United States; Recruiting
Andreas Reiff, MD, Phone: 323-669-2119
Andrew Atalig, Phone: 323-669-5958
Andreas Reiff, M.D., Principal Investigator
Bracha Shaham, M.D., Sub-Investigator
Karen Marzan, M.D., Sub-Investigator
Bram Bernstein, M.D., Sub-Investigator
Wendy DeLaPena, M.D., Sub-Investigator

Children's Memorial Hospital, Chicago, Illinois 60614, United States; Recruiting
Marissa Klein-Gitelman, MD, Phone: 773-880-4360
Angie Kress, Phone: 773-880-3474
Marissa Klein-Gitelmann, M.D., Principal Investigator
Jerome Lane, M.D., Sub-Investigator

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States; Recruiting
Kathleen A Haines, MD, Phone: 201-996-5306, Email: KHaines@humed.com
Kathleen A Haines, MD, Principal Investigator

Morgan Stanley Children's Hospital of New York, New York, New York 10032, United States; Recruiting
Candido Bates, Phone: 212-305-9304
Lisa Imundo, M.D, Phone: 212-305-9304
Lisa Imundo, M.D., Principal Investigator
Deborah Levy, M.D., Sub-Investigator
Philip Kahn, M.D., Sub-Investigator

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States; Recruiting
Shannen L Nelson, RN, BSN, Phone: 513-636-5484, Email: Shannen.Nelson@cchmc.org
Hermine I Brunner, M.D. M.Sc, Phone: 513-636-7275, Email: hermine.brunner@cchmc.org
Brent T Graham, M.D., Sub-Investigator
Daniel Lovell, M.D., Sub-Investigator
Hermine Brunner, M.D., Principal Investigator

Columbus Children's Hospital, Columbus, Ohio 43205, United States; Recruiting
Gloria Higgins, PhD, MD, Phone: 614-722-5525
Rob Rennebohm, M.D., Phone: 614-722-5525
Gloria Higgins, M.D., Principal Investigator
Rob Rennebohm, M.D., Sub-Investigator

Children's Hospital of Oklahoma, Oklahoma City, Oklahoma 73104, United States; Recruiting
Kathleen O'Neil, MD, Phone: 405-271-7086, Email: Kathleen-O'Neil@ouhsc.edu
Kathleen O'Neil, MD, Principal Investigator
James Jarvis, MD, Sub-Investigator

Seattle Children's Hospital, Seattle, Washington 98105, United States; Recruiting
Carol Wallace, MD, Phone: 206-987-4448, Email: carol.wallace@seattlechildrens.org
Stephanie Hamilton, RN, Phone: 206-987-4558, Email: stephanie.hamilton@seattlechildrens.org
Laurie O Bietz, MD, Sub-Investigator
Carol Wallace, MD, Principal Investigator
Anne M Stevens, MD, Sub-Investigator
Troy Torgerson, MD, Sub-Investigator

Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States; Terminated

Starting date: June 2003
Last updated: September 19, 2007