Clinical trial NCT01160315: Efficiency of Gonadotropin-releasing Hormone (GnRH) Agonist in Preventing Chemotherapy Induced Ovarian Failure
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Fertility Preservation
Alkylating Agents
Lymphoma
Keywords: ovarian failure, chemotherapy, lymphoma, GnRH agonist
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
Collaborators: name: Fonds National de la Recherche Scientifique
name: Ipsen
First posted: 2010-07-12
Enrollment: 118
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Premature ovarian failure rate
timeFrame: 5 years
Secondary outcomes:
measure: Impact of the flare-up effect of Triptorelin
timeFrame: 2 years
measure: Ovarian function during the treatment
timeFrame: 1 year
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 1 year
measure: Add back therapy effect
timeFrame: 1 year
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Algemeen Ziekenhuis Stuivenberg
city: Brugges
country: Belgium
facility: AZ St Jan
city: Brussels
country: Belgium
facility: Bordet
city: Brussels
country: Belgium
facility: Erasme Hospital
city: Brussels
country: Belgium
facility: AZ-VUB
city: Brussels
country: Belgium
facility: St Luc University
city: Lille
country: Belgium
facility: CHRU Lille
city: Dijon
country: France
facility: CHU Dijon
city: Nancy
country: France
facility: CHU Nancy
city: Paris-Creteil
country: France
facility: Henry-Mondor Hospital
city: Paris
country: France
facility: Hôpital Hotel Dieu
city: Paris
country: France
facility: St Louis Hospital
city: Paris
country: France
facility: CHU St Antoine
city: Rouen
country: France
facility: Centre Henri Beckerel
city: Milano
country: Italy
facility: Instituto Europeo di oncologia
Study officials:
affiliation: Erasme hospital
name: Yvon Englert, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Demeestere I, Brice P, Peccatori FA, Kentos A, Gaillard I, Zachee P, Casasnovas RO, Van Den Neste E, Dechene J, De Maertelaer V, Bron D, Englert Y. Gonadotropin-releasing hormone agonist for the prevention of chemotherapy-induced ovarian failure in patients with lymphoma: 1-year follow-up of a prospective randomized trial. J Clin Oncol. 2013 Mar 1;31(7):903-9. doi: 10.1200/JCO.2012.42.8185. Epub 2012 Nov 5.