A Prospective Open Randomized Trial on the Efficacy of Gonadotropin-releasing Hormone Agonist Depot-Triptorelin- to Prevent Chemotherapy Induced Premature Ovarian Failure in Lymphoma Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 15
- 主要终点
- Premature ovarian failure rate
研究概览
简要总结
Chemotherapy drugs like alkylating agents are frequently used in various combined regimens to treat neoplastic and benign diseases. These drugs are definitely associated with premature ovarian failure (POF), resulting in an important decrease of the long-term quality of life and an increase of morbidity. A recent study showed that the patients treated by alkylating agents had a 4.52 fold higher risk to lose their ovarian function compared with those who were treated by other agents. The rate of POF after treatment ranged from 40 to 80%, according to the age of the patients and the total doses administered.
Young women who experience POF have to face with the prospects of infertility and to consider years of hormonal replacement therapy. The possibility of minimizing gonadal damage by administering of protective therapy during chemotherapy represents an attractive option for these patients.
The aim of this study is to evaluate the protective effect on the ovarian function of the gonadotropin-releasing hormone agonist (GnRha) administered concomitantly to alkylating agents. Preliminary data in the literature on animals (rat and monkeys) are promising. Data in human are, however, highly controversial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women between 18 and 45 years old with lymphoma.
- •Menarche >2year
- •Subject treated by chemotherapy-induced ovarian failure including alkylant agents (except less than 8 ABVD)
- •Presence of both ovaries (ovarian biopsy or hemiovariectomy for cryopreservation before treatment is accepted).
- •Ability to give written informed consent
排除标准
- •Hormonal-sensible malignancy
- •Chemotherapy or radiotherapy before the inclusion in the study
- •Pelvic irradiation including the ovaries or TBI
- •Pregnancy
- •Patient weight above 110 kg
- •Anamnesis of thrombo-embolic processes
- •Severe hepatic or renal insufficiency
- •Systolic blood pressure >15mmHg or diastolic blood pressure > 90mmHg
- •Contraindication of IM injection
- •Relevant ovarian abnormalities (Functional follicular cyst are tolerated)
- •Anamnesis of premature ovarian failure or irregular cycle (repeated amenorrhoea >2 months)
- •Dubin-Johnson and Rotor Syndrome
研究组 & 干预措施
Arm A (GnRha arm)
IM injection of Triptorelin -Decapeptyl PR 11.25mg- (every 3 months) and Norethisterone acetate- Primolut-Nor 5 mg- per os continuously until the end of the chemotherapy
干预措施: Triptorelin (Drug)
Arm A (GnRha arm)
IM injection of Triptorelin -Decapeptyl PR 11.25mg- (every 3 months) and Norethisterone acetate- Primolut-Nor 5 mg- per os continuously until the end of the chemotherapy
干预措施: Norethisterone acetate (Drug)
Arm B (control Arm)
Norethisterone acetate alone, 5mg par day, (ARM B) until the end of the chemotherapy.
干预措施: Norethisterone acetate (Drug)
结局指标
主要结局
Premature ovarian failure rate
时间窗: 5 years
Primary endpoint is to evaluate the short and long-term efficacy of triptorelin depot plus progestin versus progestin alone to prevent POF induced by chemotherapy treatment. The ovarian function (FSH, E2, Progesterone, and AMH, presence of spontaneous menstrual cycle and pregnancies) will be evaluated every 3 months during the first 6 months after the end of chemotherapy, every 6 months during the next 18 months and once a year during an additional 5 years. All hormonal treatment has to be interrupted 10 days before the blood test.
次要结局
- Impact of the flare-up effect of Triptorelin(2 years)
- Ovarian function during the treatment(1 year)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(1 year)
- Add back therapy effect(1 year)