A Multicenter Open-label Clinical Study on the Prevention of Premature Ovarian Failure After HSCT

Study Overview
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Brief Summary
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HSCT is an effective method to cure hematologic malignancies. However, the reproductive system is prone to be damaged during radiotherapy and chemotherapy before transplantation, leading to ovarian failure, followed by infertility and premature ovarian failure (POF), which seriously affect the long-term quality of life of patients. This clinical trial aimed to observe the effect of Gonadotropin-releasing hormone analogues (GnRHa) on ovarian function in women of reproductive age after HSCT, so as to provide clinical evidence for whether GnRHa should be used for the prevention of POF.

Detailed Description
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Hematopoietic stem cell transplantation (HSCT) is an effective method for the treatment of hematologic malignancies. However, in the process of radiotherapy and chemotherapy before transplantation, the reproductive system is vulnerable to damage, leading to ovarian failure, which leads to infertility and premature ovarian failure (POF), seriously affecting the long-term quality of life of patients. Exogenous injection of gonadotropin-releasing hormone analogue (GnRHa) has a significant effect on fertility preservation in adolescent and reproductive female patients with breast cancer and cervical cancer. However, there is a lack of large-scale clinical studies on POF in HSCT. Therefore, this clinical trial aimed to observe the effect of GnRHa application before transplantation on ovarian function in women of reproductive age after transplantation, so as to provide clinical evidence for whether GnRHa application for fertility function protection.

Official Title
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A Multicenter Open-label Clinical Study on the Prevention of Premature Ovarian Failure After Hematopoietic Stem Cell Transplantation

Conditions
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Hematopoietic Stem Cell Transplantation, Premature Ovarian Failure

Intervention / Treatment
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* Drug: leuprorelin
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with acute leukemia, MDS, lymphoma, multiple myeloma, SAA and other hematological diseases, with the indications for autologous or allogeneic hematopoietic stem cell transplantation. Female, aged 18-45 years. Ovarian function was normal before treatment. Volunteer to participate in clinical research and sign the informed consent form. Exclusion Criteria: No menstruation before treatment, undergone hysterectomy or ovarian surgery. Abnormal sexual development. Received radiotherapy. Combined with tumors affecting gonadal function. Deep vein thrombosis. Hypertension, liver and/or kidney dysfunction cannot tolerate hematopoietic stem cell transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leprorelin group<br>Leprorelin was given subcutaneously before each cycle of chemotherapy. | Drug: leuprorelin<br>* From the initial chemotherapy after diagnosis, patients received a subcutaneous injection of leprorelin in each cycle of chemotherapy including the conditioning treatment prior to transplantation.<br>* Other names: GnRHa;|
| Placebo Comparator: Control group<br>Normal salinewas given subcutaneously before each cycle of chemotherapy. | Drug: normal saline<br>* From the initial chemotherapy after diagnosis, patients received a subcutaneous injection of normal saline in each cycle of chemotherapy including the conditioning treatment prior to transplantation.<br>* Other names: NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| POF rate | Incidence of premature ovarian failure after transplantation | three years after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute GVHD rate | the incidence of acute graft-versus-host disease (GVHD) | At day 100 post-transplantation | 
| chronic GVHD rate | the incidence of chronic graft-versus-host disease (GVHD) | From date of HSCT until the end of follow-up or the date of death from any cause, whichever came first,assessed up to 36 months. | 
| PFS | Progression Free Survival | From date of HSCT until the end of follow-up or the date of death from any cause, whichever came first，assessed up to 36 months. | 
| OS | Overall Survival | From date of diagnosis until the end of follow-up or the date of death from any cause, whichever came first，assessed up to 36 months. | 
| AEs | Adverse reations include abnormalities in bone mineral density, blood glucose, liver and kidney functions. | up to 6 months after HSCT |