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

Lupus Erythematosus, Systemic Clinical Trial

— LUPRON  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01257802
• Other study ID #: HUM00043071
• Status: Terminated
• Phase: Phase 3
• First received: December 9, 2010
• Last updated: May 11, 2016
• Start date: May 2011
• Est. completion date: November 2015

Study information

• Verified date: May 2016
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Isolated Angiitis of Central Nervous System
• Lung Disease Interstitial Diffuse
• Lung Disease With Systemic Sclerosis
• Lung Diseases
• Lung Diseases, Interstitial
• Lupus Erythematosus, Systemic
• Rheumatic Diseases
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Vasculitis
• Vasculitis

Intervention

Drug:
• 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
• Placebo
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

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	The Ohio State University	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Joseph Mccune	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Proportion of patients with AMH of =1.0 ng/mL vs >1 ng/mL, presence of menses, presence of either an AMH level of >1 ng/mL OR antral follicle count of >4. Continuous measures include: antral follicle count (AFC), ovarian volume, and FSH.		Various, per protocol	No