AMH as a Predictor of Infertility Risk in Children With Cancer (CHANCE)

Recruiting

• Conditions: Gonadotropin-releasing Hormone Agonist; Fertility Preservation; Pediatrics Cancer; Lymphoma
• Interventions: Other: No intervention

• Registration Number: NCT02595255
• Lead Sponsor: Erasme University Hospital

Brief Summary

While most of the children spontaneously recover menstruation or experienced normal puberty after chemotherapy, their ovarian reserve may be impaired by treatment inducing future infertility. Fertility preservation is currently proposed for selected prepubertal patients with a high risk of premature ovarian failure after treatment (mostly conditioning regimen for bone marrow transplantation). For patients with low or moderate risks, counselling is very difficult and no fertility preservation procedure is usually proposed for these patients as no marker of the ovarian reserve has been validated in this young population to assess the individual risk.

The primary objective of the study is to prevent long-term treatment-related infertility by detecting the young patients who normally progressed to menarche but have a reduced ovarian reserve. These patients may benefit from particular follow-up and fertility preservation procedure.

Detailed Description

In this clinical trial, we will prospectively evaluate the AMH (Antimüllerian Hormone) level before and after treatment (up to 18 years old) in a large cohort of pre- and post-pubertal children treated for cancer. The children enrolled are young patients between 3 and 14 year old who are newly diagnosed with cancer or benign diseases treated by chemotherapy and/or pelvic irradiation. They belong to one of these 3 groups (modified from Wallace et al, 2005):

* High risk

* Moderate/Low risk

* No risk (control group)

Primary endpoint:

Evaluate AMH as a potential biomarker of ovarian reserve in prepubertal/pubertal girl treated by chemotherapy (classified according to the AAD(Alkylating Agent Dose) score)

Secondary endpoints:

* Evaluate the association between the post-treatment ovarian reserve and the AMH pretreatment values in patients considered as moderate or low risk.

* Identify new patients group who may benefit from fertility preservation

* Compare the gonadotoxicity of chemotherapy regimen according to the pubertal status.

* Study the relation between the AMH levels and the pubertal age, menstruation cycle regularity, hormonal levels (FSH (follicle stimulating hormone), œstradiol, and testosterone) and bone age.

Different parameters will be assessed at inclusion, end of the treatment and during the follow-up (every year during the first 3 years and then every 2 years until the end of the study) Oncological outcome The patients will be followed up for progression and survival as per standard local practice.

Ovarian reserve and function:

Ovarian reserve will be evaluated based on hormonal dosages at different times of the study: FSH, AMH, estradiol, testosterone and LH (luteinizing hormone). Menstrual function will be evaluated by collecting information of the pubertal status (spontaneous or induced puberty) and menstrual cycle characteristics

Puberty evaluation:

All children will have an evaluation of the TANNER pubertal stage at 9 years of age (or later if \> 9 years old at the time of inclusion) and once a year until the end of puberty (when patients reach Tanner stage 5). An X-ray of the left hand and wrist will be carried out for bone age evaluation at 9-11 and 13 years old.

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2015-11-02
• Study First Submitted QC: 2015-11-02
• Study First Posted: 2015-11-03
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-30
• Last Update Posted: 2020-05-04
• Primary Completion: 2021-12
• Study Completion: 2036-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 275

Inclusion Criteria

• Patients from 3 to 14 year old included - Belong to one of these 3 groups (modified from Wallace et al, 2005):

  • High risk : Conditioning therapy for bone marrow transplantation or pelvic irradiation
  • Moderate/Low risk : Pathologies treated with chemotherapy regimen with moderate or low risk of inducing ovarian function insufficiency: AML, osteosarcoma, Ewing sarcoma, neuroblastoma, non-Hodgkin lymphoma, Hodgkin lymphoma, soft tissue sarcoma, ALL, Wilms tumour, retinoblastoma.
  • No risk (control group) : patients with chronic benign diseases or malignancies who don't receive any chemotherapy or other gonadotoxic treatment.

Exclusion Criteria

• CNS (central nervous system) irradiation, cerebral tumour
• Current or previous ovarian disease/surgery
• Familial history of premature ovarian failure (no iatrogenic or surgical origins)
• Previous known severe chronic disease potentially affecting normal growth or puberty (diseases inducing malnutrition, anorexia, genetic/congenital disorders as Turner, Kallman, BPES(Blepharophimosis, ptosis, and epicanthus inversus syndrome) syndromes, uncontrolled severe diabetes, Cushing Syndrome, auto-immune diseases, cystic fibrosis, severe renal dysfunction)
• Genetic/congenital disorders inducing mental retardation

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
High risk	No intervention	Conditioning therapy for bone marrow transplantation or pelvic irradiation. Fertility preservation is usually already proposed in this group of patients. No intervention.
Moderate/low risk	No intervention	Pathologies treated with chemotherapy regimen with moderate or low risk of inducing ovarian function insufficiency: AML (Acute myeloide leukemia), osteosarcoma, Ewing sarcoma, neuroblastoma, non-Hodgkin lymphoma, Hodgkin lymphoma, soft tissue sarcoma, ALL (acute lymphoblastic hormone), Wilms tumour, retinoblastoma. This is the study group we will compare with high risk and no risk patients. No intervention
No risk	No intervention	Patients with chronic benign diseases or malignancies who don't receive any chemotherapy or other gonadotoxic treatment. No intervention

Primary Outcome Measures

Name	Time	Method
AMH marker	screening, 1 year after screening, every year during the first 3 year of follow-up, every 2 years until 18 year old	Blood test collection for serum storage. AMH values will be compared in the different groups and correlated with the cumulative doses of alkylating agents

Secondary Outcome Measures

Name	Time	Method
Ovarian reserve	screening, 1 year after screening, every year during the first 3 year of follow-up, every 2 years until 18 year old	relation between the AMH levels, pubertal age, menstruation cycle regularity, hormonal levels (FSH, œstradiol, and testosterone at 16 year old) and bone age
Premature ovarian failure (POF)	screening, 1 year after screening, every year during the first 3 year of follow-up, every 2 years until 18 year old	Blood test collection for serum storage. FSH, E2 and AMH measurement and pubertal status. POF rate will be compared between groups

Trial Locations

Locations (10)

Centre Hospitalier Régional (CHR)-Citadelle; 🇧🇪 Liège, Belgium

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Hospitalier Chrétien (CHC)- Clinique de l'espérance; 🇧🇪 Montegnée, Liège, Belgium

Universitair Ziekenhuis Leuven; 🇧🇪 Leuven, Belgium

Hôpital Universitaire Reine Fabiola (HUDERF); 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Brussels; 🇧🇪 Brussels, Belgium

UZ-Gent; 🇧🇪 Ghent, Belgium

Hôpital Robert Debré; 🇫🇷 Paris, France

Universitair Ziekenhuis Antwerpen; 🇧🇪 Anvers, Belgium

CHRU Lille-Hôpital Jeanne de Flandre; 🇫🇷 Lille, France