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)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01343368

Enrollment

Registered

2011-04-28

Start date

2011-07-31

Completion date

2015-04-30

Last updated

2017-12-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Post-menarchal

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.

Interventions

DRUGLeuprolide

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

BIOLOGICALhematopoietic cell transplant

Conventional bone marrow transplant regimen.

BIOLOGICALreduced 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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

50 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Comparison of Follicle Stimulating Hormone (FSH) Levels	Baseline	Comparison of treatment arms; interventional versus observational average FSH levels.
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 Lutineizing Hormone (LH) Levels	Baseline	Comparison of treatment arms; interventional versus observational average LH levels during study.
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 Antimullerian Hormone (AMH) Levels After Transplant	Day Prior to Transplant	Comparison of treatment arms; interventional versus observational average AMH levels after receiving transplant.
Comparison of Luteinizing Hormone (LH) Levels	Day 100	Comparison of treatment arms; interventional versus observational average LH levels during study.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. 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 hematopoietic cell transplant: Conventional bone marrow transplant regimen.	7
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. 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.	10
Total	17

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	1	0
Overall Study	Lost to Follow-up	1	0

Baseline characteristics

Characteristic	Interventional - Received Leuprolide	Observational Arm	Total
Age, Categorical <=18 years	2 Participants	6 Participants	8 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	5 Participants	4 Participants	9 Participants
Sex: Female, Male Female	7 Participants	10 Participants	17 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 7	0 / 10
serious Total, serious adverse events	0 / 7	0 / 10

Outcome results

Primary

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.

Time frame: Through Day 180 Post Transplant

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Interventional - Received Leuprolide	Comparison of Number of Patients With Ovarian Failure	3 Participants
Observational Arm	Comparison of Number of Patients With Ovarian Failure	1 Participants

Secondary

Comparison of Antimullerian Hormone (AMH) Levels After Transplant

Comparison of treatment arms; interventional versus observational average AMH levels after receiving transplant.

Time frame: Day 180 after Transplant

Population: Four patients on the Observational and 10 patients on the Observational arm never had any follow-up AMH levels drawn and were removed from this analysis.

Arm	Measure	Value (MEAN)	Dispersion
Interventional - Received Leuprolide	Comparison of Antimullerian Hormone (AMH) Levels After Transplant	0.08 ng/ml	Standard Deviation 0

Secondary

Comparison of Antimullerian Hormone (AMH) Levels After Transplant

Comparison of treatment arms; interventional versus observational average AMH levels after receiving transplant.

Time frame: Day Prior to Transplant

Population: Six patients on the Observational arm never had any follow-up AMH levels drawn and were removed from this analysis.

Arm	Measure	Value (MEAN)	Dispersion
Interventional - Received Leuprolide	Comparison of Antimullerian Hormone (AMH) Levels After Transplant	0.6 ng/ml	Standard Deviation 0.9
Observational Arm	Comparison of Antimullerian Hormone (AMH) Levels After Transplant	6.4 ng/ml	Standard Deviation 7.7

Secondary