Preservation of Ovarian Function After Hematopoietic Cell Transplant

A Phase II Trial of GnRH Agonist for the Preservation of Ovarian Function After Hematopoietic Cell Transplantation (HCT)

Women undergoing myeloablative allogeneic hematopoietic cell transplant (MA HCT) will receive GnRH agonist leuprolide. Women undergoing reduced intensity allogeneic (RIC) HCT will be observed.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Myeloproliferative Disorders; Multiple Myeloma; Hodgkin Disease; Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Leuprolide; Biological: hematopoietic cell transplant; Biological: reduced intensity allogeneic HCT

Detailed Description

This study is to use gonadotropin releasing hormone (GnRH) agonist leuprolide prior myeloablative hematopoietic cell transplantation to prevent ovarian dysfunction in post-menarchal women.

The primary objective is to determine the effect of GnRH agonists on the incidence of ovarian failure.

The secondary objectives are

• to determine how effective GnRH agonists are at suppressing menses during
• to determine the incidence and timing of resumption of menstrual cycles after HCT
• to determine the incidence and timing of resumption of normal FSH and LH levels after HCT
• to determine the incidence of normal AMH levels after HCT
• to determine the effect of GnRH agonists on immune reconstitution after HCT
• to assess the safety and tolerability of GnRH agonists in the context of HCT

A total of 47 patients will be accrued in this study.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Interventional Arm:

  • Eligible for myeloablative allogenic or autologous hematopoietic cell transplant (HCT)
  • Post-menarchal female < or = 50 years of age
  • Normal antimullerian hormone (AMH) level and/or follicle stimulating hormone (FSH)/leuprolide (LH) levels for age/stage of puberty
  • Those women who have an FSH > 40 IU/L and whose diagnosis of malignancy and whose chemotherapy treatment was within 12 weeks of enrollment are still eligible if they had normal menstrual cycles pre-diagnosis.

• Observational Arm:

  • Eligible for reduced intensity allogeneic HCT
  • Post-menarchal female ≤ 50 years of age
  • Normal AMH level and/or FSH/LH for age/stage of puberty
  • Those women who an FSH >40 IU/L and whose diagnosis of malignancy and chemotherapy treatment was within 12 weeks of enrollment are still eligible if they had normal menstrual cycles pre-diagnosis.

Exclusion Criteria:

• All Arms:

  • History of ovarian cancer
  • Surgical resection of one or both ovaries. Prior hysterectomy is allowed as long as the ovaries are intact.
  • Use of GnRH agonist in last 12 months will exclude patients if lab results are not available to demonstrate adequate ovarian function prior to initiation of GnRH therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Interventional - Received Leuprolide; Long-acting leuprolide 11.25 mg intramuscularly (IM) pre-HCT and 3 months post-HCT PLUS Short-acting leuprolide 0.2 mg subcutaneously (SQ) daily for 14 days for patients who undergo myeloablative allogeneic or autologous hematopoietic cell transplantation.	Drug: Leuprolide; Long-acting leuprolide 11.25 mg intramuscularly (IM) pre-transplant (HCT) and 3 months post-HCT PLUS Short-acting leuprolide 0.2 mg subcutaneously (SQ) daily for 14 days; Other Names: Leuprolide acetate; Lupron Depot-3(R); Biological: hematopoietic cell transplant; Conventional bone marrow transplant regimen.; Other Names: HCT
ACTIVE_COMPARATOR: Observational Arm; Women undergoing reduced intensity allogeneic HCT will be observed. Progestin contraceptives, Norethindrone acetate, and any other hormone methods can be used according to the prescription guidelines except for GnRH agonists to suppress menses.	Biological: reduced intensity allogeneic HCT; A reduced-intensity conditioning transplant is a bone marrow or cord blood transplant (also called a BMT) that uses less intense treatment to prepare for transplant than a standard transplant does. While a standard transplant uses the pre-transplant treatment to destroy most of the disease cells, a reduced-intensity transplant relies on the donor's immune cells to fight disease.; Other Names: RIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Number of Patients With Ovarian Failure	Comparison of treatment arms; interventional versus observational. Ovarian failure rate is based on FSH measured at 180 days after HCT; to determine the effect of GnRH agonists on the incidence of ovarian failure (i.e. FSH >40 IU/L) after transplant.	Through Day 180 Post Transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Number of Patients Who Stopped Menstrual Bleeding	Comparison of treatment arms; interventional versus observational. Count of patients who stopped menstrual bleeding; to determine how the effect of GnRH agonists are at suppressing menses during hematopoietic cell transplant	From Baseline Through Day 365
Comparison of Follicle Stimulating Hormone (FSH) Levels	Comparison of treatment arms; interventional versus observational average FSH levels.	Baseline
Comparison of Follicle Stimulating Hormone (FSH) Levels	Comparison of treatment arms; interventional versus observational average FSH levels.	Day 100
Comparison of Follicle Stimulating Hormone (FSH) Levels	Comparison of treatment arms; interventional versus observational average FSH levels.	Day 180
Comparison of Follicle Stimulating Hormone (FSH) Levels	Comparison of treatment arms; interventional versus observational average FSH levels.	1 year
Comparison of Follicle Stimulating Hormone (FSH) Levels	Comparison of treatment arms; interventional versus observational average FSH levels.	2 years
Comparison of Number of Patients Who Resumed Menstrual Cycles	Comparison of treatment arms; interventional versus observational. Count of patients who resumed menses after hematopoietic cell transplant	Day 365 Post Transplant
Comparison of Lutineizing Hormone (LH) Levels	Comparison of treatment arms; interventional versus observational average LH levels during study.	Baseline
Comparison of Luteinizing Hormone (LH) Levels	Comparison of treatment arms; interventional versus observational average LH levels during study.	Day 100
Comparison of Luteinizing Hormone (LH) Levels	Comparison of treatment arms; interventional versus observational average LH levels during study.	Day 180
Comparison of Luteinizing Hormone (LH) Levels	Comparison of treatment arms; interventional versus observational average LH levels during study.	1 year
Comparison of Leuprolide Hormone (LH) Levels	Comparison of treatment arms; interventional versus observational average LH levels during study.	2 years
Comparison of Antimullerian Hormone (AMH) Levels After Transplant	Comparison of treatment arms; interventional versus observational average AMH levels after receiving transplant.	Day Prior to Transplant
Comparison of Antimullerian Hormone (AMH) Levels After Transplant	Comparison of treatment arms; interventional versus observational average AMH levels after receiving transplant.	Day 180 after Transplant

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: Minnesota Medical Foundation

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: March 15, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (ESTIMATE): April 28, 2011

Study Record Updates

• Last Update Posted (ACTUAL): December 5, 2017
• Last Update Submitted That Met QC Criteria: December 3, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Post-menarchal
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Lymphoma; Multiple Myeloma; Hodgkin Disease; Myeloproliferative Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: 2010LS053; 012M93555 (OTHER: Institutional Review Board, University of Minnesota)