Denosumab for Prevention of Bone Complications After Bone Marrow Transplantation in Children

St. Justine's Hospital

Status and phase: Withdrawn; Phase 1

Conditions: Disorder Related to Bone Marrow Transplantation

Treatments: Drug: Denosumab

Study type: Interventional

Funder types: Other

Identifiers

NCT02677246

HSJ001

Details and patient eligibility

About

Children treated by bone marrow transplantation (BMT) experience bone toxicity. Those bone damages are caused by both a decrease of bone formation and an increase of bone destruction after BMT.For long term survivors, bone complications are major determinants of impaired quality of life. No standard treatment currently exists to prevent those bone injuries. Denosumab is a treatment which specifically blocks bone destruction for 4 to 6 months in adults. This trial will study whether it is safe to prescribe Denosumab to children after BMT in the aim of preventing bone complications.

Full description

Participant will receive one subcutaneous dose of Denosumab within 2 weeks after confirmation of bone marrow engraftment. The dose of treatment will be escalated between participants. Denosumab is supposed to be effective for several months (4 to 6 months). The biologic activity of Denosumab will be followed by the measure in the blood of a biomarker of bone destruction called CTX. This biomarker is supposed to decrease after Denosumab infusion, reflecting the blockade of bone destruction by the treatment. Bone density will be assessed by a radiologic test named DXA which a standard test. All blood and radiologic tests mandated by the study will be done at the same time as standard follow-up after bone marrow transplant. Thus, participants will not have extra visits at the outpatient clinic, or extra blood punctures, for the specific purpose of the study. Participants will be followed for 36 months after bone marrow transplantation.For experiencing graft versus host disease, a second dose of Denosumab will be allowed, followed by subsequent doses evry 4 to 6 months till a maximum of 4 doses within 24months after bone marrow transplantation.

Sex: All

Ages: 2 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age from 2 year to 21 years
• Allogenic hematopoietic stem cell transplantation (allo-HSCT) planned within 1 month.
• Informed consent signed by participant more than 18 year old, or parents or his/her legal guardian
• Teeth examination by a dentist in order to rule out or to treat latent teeth infections before allo-HSCT

Exclusion criteria

• Refusal of signing informed consent
• Prior inclusion in another therapeutic trial with a time elapsed from the last research drug dose to Denosumab, shorter than 7 half-lifes of the research drug
• Osteopetrosis
• Bisphosphonates treatment within 12 months before entering the trial
• Tooth infection not treated before allo-HSCT
• Child-bearing and breastfeeding women

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Denosumab

Experimental group

Description:

Phase 1, 3+3 design with inter-patient dose escalation from 1mg/kg/dose to 2mg/kg/dose, and possibility of a dose de-escalation of 0.5mg/kg/dose, A modification of 3+3 design is implemented to take into account the achievement of bone resorption blockade by Denosumab. CTX is a biologic marker of bone resorption. Provided a decrease of CTX blood level will be observed under the lower limit (2,5th percentile) for age and sex, or under 20% of the pre-treatment level, there will be no reason to continue escalating the dose. This modified 3+3 design prevents exposure of children to dose escalations that would not be needed regarding the medical and biological aims of this trial.

Treatment:

Drug: Denosumab