Intervention: Leuprolide Acetate
Trial phase: Phase 3
SMILES: CC(=O)O.CCNC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(Cc1c[nH]c2ccccc12)NC(=O)C(Cc1cnc[nH]1)NC(=O)C1CCC(=O)N1
Sex: Female
Age groups: Adult
Healthy volunteers: No
Participants at risk: 6
Group description: depot leuprolide acetate 3.75 mg: Monthly depot leuprolide acetate 3.75 mg vs placebo 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
Eligibility criteria:
Female, post menarche, not menopausal
Ages 18-40 years inclusive at enrollment

Diagnosis consistent with a rheumatic or autoimmune disease requiring 3-6 months of daily or intermittent cyclophosphamide therapy. This may include, but is not limited to:

Systemic lupus
Sjogren's syndrome
Systemic vasculitis
Isolated vasculitis of the central nervous system
Other autoimmune neurologic diseases requiring cyclophosphamide including transverse myelitis, peripheral neuropathies, multiple sclerosis, neuromyelitis optica, and retinal vasculitis
Behcet's syndrome
Scleroderma
Inflammatory myositis
Interstitial lung disease, other autoimmune pulmonary diseases requiring cyclophosphamide
Overlap connective tissue diseases not precisely fitting the above definitions clearly requiring cyclophosphamide for severe immune mediated organ damage
Rheumatoid vasculitis

Patients will have planned cyclophosphamide treatment according to any one of the following regimens:

3 to 6 months of daily oral cyclophosphamide: Lupron/placebo must be given within four (4) weeks of initiation of daily cyclophosphamide.
The Eurolupus regimen consisting of 6 fortnightly biweekly boluses of 500 mg cyclophosphamide: First dose of Lupron/placebo must be given 10 days prior to the second dose of cyclophosphamide
3 to 6 monthly boluses of cyclophosphamide by the NIH regimen: First dose of Lupron/placebo must be given 10 days prior to the second dose of cyclophosphamide
A satisfactory plan for contraception consistent with cyclophosphamide administration (when appropriate: depot progestins, IUD, combination oral contraception and/or dual barrier contraception).

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.