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

NCT ID: NCT02595255

Last Updated: 2020-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

275 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-04-30

Study Completion Date

2036-12-31

Brief Summary

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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

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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.

Conditions

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Fertility Preservation Lymphoma Pediatrics Cancer Gonadotropin-releasing Hormone Agonist

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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High risk

Conditioning therapy for bone marrow transplantation or pelvic irradiation. Fertility preservation is usually already proposed in this group of patients. No intervention.

No intervention

Intervention Type OTHER

No intervention

Moderate/low risk

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 intervention

Intervention Type OTHER

No intervention

No risk

Patients with chronic benign diseases or malignancies who don't receive any chemotherapy or other gonadotoxic treatment.

No intervention

No intervention

Intervention Type OTHER

No intervention

Interventions

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No intervention

No intervention

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

3 Years

Maximum Eligible Age

14 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Queen Fabiola Children's University Hospital

OTHER

Sponsor Role collaborator

Erasme University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Isabelle Demeestere, PhD

Role: STUDY_DIRECTOR

Erasme ULB- Belgium

Alina Ferster

Role: PRINCIPAL_INVESTIGATOR

Queen Fabiola children's university hospital- Belgium

Christine Decanter

Role: PRINCIPAL_INVESTIGATOR

CHRU Lille, France

Locations

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Centre Hospitalier Chrétien (CHC)- Clinique de l'espérance

Montegnée, Liège, Belgium

Site Status RECRUITING

Universitair Ziekenhuis Antwerpen

Antwerp, , Belgium

Site Status RECRUITING

Hôpital Universitaire Reine Fabiola (HUDERF)

Brussels, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Brussels

Brussels, , Belgium

Site Status RECRUITING

UZ-Gent

Ghent, , Belgium

Site Status NOT_YET_RECRUITING

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status RECRUITING

Centre Hospitalier Régional (CHR)-Citadelle

Liège, , Belgium

Site Status RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status RECRUITING

CHRU Lille-Hôpital Jeanne de Flandre

Lille, , France

Site Status RECRUITING

Hôpital Robert Debré

Paris, , France

Site Status NOT_YET_RECRUITING

Countries

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Belgium France

Central Contacts

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Isabelle Demeestere, PhD

Role: CONTACT

+32 2 555 65 92

Julie Dechene

Role: CONTACT

+32 2 555 63 58

Facility Contacts

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Morgan Collin

Role: primary

+32 4 224 91 42

Hanna Ryckaert

Role: primary

+32 3 821 58 39

Merry Vanpuyvelde

Role: primary

+32 2 477 38 85

Bernard Wenderickx

Role: backup

+32 2 477 36 54

Wiert Robberechts

Role: primary

+32 2 801 28 14

Els Vandecruys

Role: primary

Jemima Gaytant

Role: primary

+32 16 34 37 63

Catherine Sondag

Role: primary

+32 4 321 89 77

Sandy Vandermeersch

Role: primary

+33 3 20 29 58 26

Cécile Veron

Role: primary

+33 3 20 44 60 58

Jean-Hugue Dalle

Role: primary

References

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Brougham MF, Crofton PM, Johnson EJ, Evans N, Anderson RA, Wallace WH. Anti-Mullerian 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.

Reference Type BACKGROUND
PMID: 22472563 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25130994 (View on PubMed)

Demeestere I, Simon P, Dedeken L, Moffa F, Tsepelidis 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.

Reference Type BACKGROUND
PMID: 26062556 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24958067 (View on PubMed)

Other Identifiers

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CHANCE (CHildren, Amh, caNCEr)

Identifier Type: -

Identifier Source: org_study_id

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