GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases
Condition: Lupus Erythematosus, Systemic; Systemic Vasculitis; Isolated Angiitis of Central Nervous System; Lung Disease With Systemic Sclerosis; Lung Disease Interstitial Diffuse
MeSH terms: Rheumatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Vasculitis; Systemic Vasculitis; Scleroderma, Systemic; Collagen Diseases; Lupus Erythematosus, Systemic
Intervention: depot leuprolide acetate 3.75 mg; Placebo
Intervention description: 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; Monthly 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
Intervention MeSH terms: Leuprolide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 14.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        1. Female, post menarche, not menopausal

          2. Ages 18-40 years inclusive at enrollment

          3. 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

          4. 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

          5. A satisfactory plan for contraception consistent with cyclophosphamide administration
             (when appropriate: depot progestins, IUD, combination oral contraception and/or dual
             barrier contraception).

        Exclusion Criteria:

          1. Symptoms consistent with ovarian failure based on gynecologic evaluation and
             confirmatory laboratory testing

          2. Prior unilateral or bilateral oophorectomy

          3. Cervical intraepithelial neoplasia (CIN 2, or more severe), that has not been
             adequately evaluated or is not being adequately treated

          4. Contraindications to use of GnRH-a (e.g., undiagnosed abnormal uterine bleeding)

          5. Prior adverse or allergic reaction to GnRH-a

          6. A history of severe psychiatric disorders, particularly severe depression that is
             currently not adequately treated

          7. History of significant noncompliance with medical treatment

          8. 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.

          9. Pregnant or breastfeeding

         10. Significant thrombotic event requiring treatment that will not have received
             appropriate therapy for at least 4 weeks before initiation of study drug.