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

NCT01257802 | Terminated Phase 3 Results DMC

• 2 other identifiers: HUM000430715R01HD066139
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Day 0 to 6-month post-intervention visit

Secondary Outcomes (4)

• Count of Patients With AMH of ≤1.0 ng/mL vs >1 ng/mL,

  baseline and 6 months

• Number of Participants With Either an AMH Level of >1 ng/mL OR Antral Follicle Count of >4.

  baseline and 6 months

• Mean Antral Follicle Count (AFC)

  baseline and 6 months

• Mean Ovarian Volume.

  baseline and 6 months

Study Arms (2)

LUPRON

ACTIVE COMPARATOR

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

Drug: depot leuprolide acetate 3.75 mg

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

depot leuprolide acetate 3.75 mg DRUG

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

Also known as: LUPRON depot 3.75 mg

LUPRON

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joseph Mccune: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Systemic Vasculitis

Interventions

Leuprolide

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: W Joseph McCune MD Professor of Rheuntic Diseases University of Michigan
• Organization: University of Michigan

jmccune@med.umich.edu

734 936 5560

Study Officials

• William J McCune, M.D.

  Professor of Internal Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Michael H. and Marcia S. Klein Professor of Rheumatic Diseases and Director, Lupus Clinic

Study Record Dates

• First Submitted: December 9, 2010
• First Posted: December 10, 2010
• Study Start: May 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: June 27, 2017
• Results First Posted: June 27, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)