Preservation of Ovarian Function After Hematopoietic Cell Transplant

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

Detailed Description
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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.

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

Conditions
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Multiple Myeloma, Non-Hodgkin Lymphoma, Hodgkin Disease, Acute Myeloid Leukemia, Myeloproliferative Disorders

Intervention / Treatment
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* Drug: Leuprolide
* Biological: hematopoietic cell transplant
* Biological: reduced intensity allogeneic HCT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional - Received Leuprolide<br>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<br>* 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<br>* Other names: Leuprolide acetate;Biological: hematopoietic cell transplant<br>* Conventional bone marrow transplant regimen.<br>* Other names: HCT;|
| Active Comparator: Observational Arm<br>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<br>* 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.<br>* Other names: RIC;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-menarchal