Preservation of Ovarian Function After Hematopoietic Cell Transplant

Phase 2

Terminated

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

Interventions: Biological: reduced intensity allogeneic HCT
Drug: Leuprolide
Biological: hematopoietic cell transplant

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Observational Arm	reduced intensity allogeneic HCT	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.
Interventional - Received Leuprolide	hematopoietic cell transplant	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.
Interventional - Received Leuprolide	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.

Primary Outcome Measures

Name	Time	Method
Comparison of Number of Patients With Ovarian Failure	Through Day 180 Post Transplant	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.

Secondary Outcome Measures

Name	Time	Method
Comparison of Number of Patients Who Resumed Menstrual Cycles	Day 365 Post Transplant	Comparison of treatment arms; interventional versus observational. Count of patients who resumed menses after hematopoietic cell transplant
Comparison of Luteinizing Hormone (LH) Levels	1 year	Comparison of treatment arms; interventional versus observational average LH levels during study.
Comparison of Antimullerian Hormone (AMH) Levels After Transplant	Day 180 after Transplant	Comparison of treatment arms; interventional versus observational average AMH levels after receiving transplant.
Comparison of Number of Patients Who Stopped Menstrual Bleeding	From Baseline Through Day 365	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
Comparison of Leuprolide Hormone (LH) Levels	2 years	Comparison of treatment arms; interventional versus observational average LH levels during study.
Comparison of Follicle Stimulating Hormone (FSH) Levels	2 years	Comparison of treatment arms; interventional versus observational average FSH levels.
Comparison of Lutineizing Hormone (LH) Levels	Baseline	Comparison of treatment arms; interventional versus observational average LH levels during study.