GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Phase 3

Terminated

Conditions: Isolated Angiitis of Central Nervous System
Lupus Erythematosus, Systemic
Systemic Vasculitis
Lung Disease With Systemic Sclerosis
Lung Disease Interstitial Diffuse

Brief Summary: The purpose of this study it to determine whether the use of a gonadotropin releasing hormone (GnRH)-agonist (depot-leuprolide acetate) during cyclophosphamide (CYC) therapy in women with rheumatic diseases will provide greater ovarian protection than placebo.

Detailed Description: Patients will be women ages 18-40 with either a severe rheumatic disease requiring cyclophosphamide or interstitial lung disease requiring cyclophosphamide to be administered either daily orally; monthly intravenously; or intravenously every 2 weeks for 6 doses. Because cyclophosphamide treatment may be required urgently for some indications, study entry may occur before either the first or second dose of cyclophosphamide for patients receiving cyclophosphamide intravenously.

Of 16 participants who were screened, only 14 were randomized and only 7 participants actually completed the study. Due to this low number, follicle stimulating hormone (FSH) levels were not obtained.

Secondary outcome measures that are not available include presence of menses and FSH.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Symptoms consistent with ovarian failure based on gynecologic evaluation and confirmatory laboratory testing
Prior unilateral or bilateral oophorectomy
Cervical intraepithelial neoplasia (CIN 2, or more severe), that has not been adequately evaluated or is not being adequately treated
Contraindications to use of GnRH-a (e.g., undiagnosed abnormal uterine bleeding)
Prior adverse or allergic reaction to GnRH-a
A history of severe psychiatric disorders, particularly severe depression that is currently not adequately treated
History of significant noncompliance with medical treatment
Patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants that have not already been addressed with appropriate measures to preserve bone mass.
Pregnant or breastfeeding
Significant thrombotic event requiring treatment that will not have received appropriate therapy for at least 4 weeks before initiation of study drug.

Arm && Interventions

Group	Intervention	Description
LUPRON	depot leuprolide acetate 3.75 mg	Monthly depot leuprolide acetate 3.75 mg injection during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses
Placebo	Placebo	Monthly placebo injection during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses.

Primary Outcome Measures

Name	Time	Method
Anti-mullerian Hormone (AMH) Measured as a Continuous Variable, Specifically Assessing the Intra-person Change From Study Entry (Day 0) to 6-month Post-intervention Visit	Day 0 to 6-month post-intervention visit	AMH was quantified in vitro a commercially available enzyme linked immunosorbent assay (ELISA) (Beckman Coulter; Marseille, France) was used for in vitro quantitative measurement of serum AMH.

Secondary Outcome Measures

Name	Time	Method
Count of Patients With AMH of ≤1.0 ng/mL vs >1 ng/mL,	baseline and 6 months	AMH level ≤1.0 predicts onset of menopause within 5 years in normal women
Number of Participants With Either an AMH Level of >1 ng/mL OR Antral Follicle Count of >4.	baseline and 6 months	An AMH level of \>1 ng/ml and/or an antral follicle count of \>4 in either ovary is a strong predictor of residual ovarian function
Mean Antral Follicle Count (AFC)	baseline and 6 months	Mean antral follicle count (AFC) is the average number of follicles counted in each of 2 ovaries
Mean Ovarian Volume.	baseline and 6 months	Mean ovarian volume reflects the preservation of ovarian tissue despite exposure to cyclophosphamide; reduced ovarian size is documented in cyclophosphamide treated patients