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

Lymphoma Clinical Trial

— CHANCE  

Official title:

Antimüllerian Hormone as a Predictor of Future Infertility Risk in Prepubertal/Pubertal Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02595255
• Other study ID #: CHANCE (CHildren, Amh, caNCEr)
• Status: Recruiting
• Start date: April 2014
• Est. completion date: December 2036

Study information

• Verified date: April 2020
• Source: Erasme University Hospital
• Contact: Isabelle Demeestere, PhD
• Phone: +32 2 555 65 92
• Email: idemeest[@]ulb.ac.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 275
• Est. completion date: December 2036
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 3 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Fertility Preservation
• Gonadotropin-releasing Hormone Agonist
• Infertility
• Lymphoma
• Pediatrics Cancer

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Anvers
Belgium	Hôpital Universitaire Reine Fabiola (HUDERF)	Brussels
Belgium	Universitair Ziekenhuis Brussels	Brussels
Belgium	UZ-Gent	Ghent
Belgium	Universitair Ziekenhuis Leuven	Leuven
Belgium	Centre Hospitalier Régional (CHR)-Citadelle	Liège
Belgium	Centre Hospitalier Chrétien (CHC)- Clinique de l'espérance	Montegnée	Liège
France	Centre Oscar Lambret	Lille
France	CHRU Lille-Hôpital Jeanne de Flandre	Lille
France	Hôpital Robert Debré	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Erasme University Hospital	Queen Fabiola Children's University Hospital

Countries where clinical trial is conducted

Belgium,  France, 

References & Publications (4)

Brougham MF, Crofton PM, Johnson EJ, Evans N, Anderson RA, Wallace WH. Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study. J Clin Endocrinol Metab. 2012 Jun;97(6):2059-67. doi: 10.1210/jc.2011-3180. Epub 2012 Apr 3. — View Citation

Demeestere I, Simon P, Dedeken L, Moffa F, Tsépélidis S, Brachet C, Delbaere A, Devreker F, Ferster A. Live birth after autograft of ovarian tissue cryopreserved during childhood. Hum Reprod. 2015 Sep;30(9):2107-9. doi: 10.1093/humrep/dev128. Epub 2015 Jun 9. — View Citation

Imbert R, Moffa F, Tsepelidis S, Simon P, Delbaere A, Devreker F, Dechene J, Ferster A, Veys I, Fastrez M, Englert Y, Demeestere I. Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. Hum Reprod. 2014 Sep;29(9):1931-40. doi: 10.1093/humrep/deu158. Epub 2014 Jun 22. — View Citation

Wallace WH, Smith AG, Kelsey TW, Edgar AE, Anderson RA. Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation. Lancet Oncol. 2014 Sep;15(10):1129-36. doi: 10.1016/S1470-2045(14)70334-1. Epub 2014 Aug 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AMH marker	Blood test collection for serum storage. AMH values will be compared in the different groups and correlated with the cumulative doses of alkylating agents	screening, 1 year after screening, every year during the first 3 year of follow-up, every 2 years until 18 year old
Secondary	Premature ovarian failure (POF)	Blood test collection for serum storage. FSH, E2 and AMH measurement and pubertal status. POF rate will be compared between groups	screening, 1 year after screening, every year during the first 3 year of follow-up, every 2 years until 18 year old
Secondary	Ovarian reserve	relation between the AMH levels, pubertal age, menstruation cycle regularity, hormonal levels (FSH, œstradiol, and testosterone at 16 year old) and bone age	screening, 1 year after screening, every year during the first 3 year of follow-up, every 2 years until 18 year old