GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases (LUPRON)

This study has been terminated.
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Joseph Mccune, University of Michigan
ClinicalTrials.gov Identifier:
NCT01257802
First received: December 9, 2010
Last updated: May 11, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Lupus Erythematosus, Systemic
Systemic Vasculitis
Isolated Angiitis of Central Nervous System
Lung Disease With Systemic Sclerosis
Lung Disease Interstitial Diffuse
Drug: depot leuprolide acetate 3.75 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 0 to 6-month post-intervention visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Various, per protocol ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: May 2011
Study Completion Date: November 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LUPRON 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
Other Name: LUPRON depot 3.75 mg
Placebo Comparator: Placebo 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
Other Name: LUPRON depot 3.75 mg
Drug: 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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01257802

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Joseph Mccune
National Institutes of Health (NIH)
Investigators
Principal Investigator: William J McCune, M.D. Professor of Internal Medicine
  More Information

Responsible Party: Joseph Mccune, Michael H. and Marcia S. Klein Professor of Rheumatic Diseases and Director, Lupus Clinic, University of Michigan
ClinicalTrials.gov Identifier: NCT01257802     History of Changes
Other Study ID Numbers: HUM00043071 
Study First Received: December 9, 2010
Last Updated: May 11, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Diseases
Scleroderma, Systemic
Scleroderma, Diffuse
Vasculitis
Rheumatic Diseases
Collagen Diseases
Lupus Erythematosus, Systemic
Systemic Vasculitis
Lung Diseases, Interstitial
Sclerosis
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Vascular Diseases
Cardiovascular Diseases
Musculoskeletal Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Leuprolide
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 25, 2016