Clinical trial NCT02677246: Denosumab for Prevention of Bone Complications After Bone Marrow Transplantation in Children
Official title: Phase 1 Trial of Denosumab for Prevention of Bone Complications After Allogenic Hematopoietic Stem Cell Transplantation in Children
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Disorder Related to Bone Marrow Transplantation
Keywords: Bone marrow transplantation
Children
Bone complications
Denosumab.
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2016-02-09
Enrollment: 0
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerable Dose (MTD)
timeFrame: MTD will be definitively established at 6 months after the last patient has been entered into the study. Given the anticipated rate of accrual, the primary outcome measure should be determined within 2 years after opening the study.
Secondary outcomes:
measure: Evolution of CTX (a biological marker of bone resorption) level in blood
timeFrame: Dosage before transplantation, before beginning Denosumab, then monthly till 6 months, then at 12 months, 18 months, 24 and 36 months after starting Denosumab
measure: Evolution of P1NP (a biological marker of bone synthesis) level in blood
timeFrame: Dosage before transplantation and before beginning Denosumab, then monthly till 6 months, then at 9 months, 12 months, 18 months, 24 months and 36 months after starting Denosumab
measure: Osteonecrosis (apart from jaw osteonecrosis)
timeFrame: At 1 year, 2 years and 3 years after bone marrow transplantation
measure: Fracture
timeFrame: At 1 year, 2 years and 3 years after bone marrow transplantation
measure: Bone Mineral Density (BMD)
timeFrame: Before bone marrow transplantation, then 6 months, 12 months, 24 months and 36 months after starting Denosumab
measure: Growth height evolution according to standardized World Health Organization growth charts for Canada
timeFrame: Measurement every 6 months till 24 months after entering the study, then yearly till 21 years of age.
measure: Dose Limiting toxicity (DLT)
timeFrame: Assessment every month till 6 months after bone marrow transplantation. For each dose level ,DLT will be established at 6 months after bone marrow transplantation of the 3rd participant entered into the cohort.
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: St. Justine 's Hospital
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Pierre Teira, MD
role: PRINCIPAL_INVESTIGATOR
References: