Denosumab for Prevention of Bone Complications After Bone Marrow Transplantation in Children
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|ClinicalTrials.gov Identifier: NCT02677246|
Recruitment Status : Not yet recruiting
First Posted : February 9, 2016
Last Update Posted : October 13, 2016
|Condition or disease||Intervention/treatment||Phase|
|Disorder Related to Bone Marrow Transplantation||Drug: Denosumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Trial of Denosumab for Prevention of Bone Complications After Allogenic Hematopoietic Stem Cell Transplantation in Children|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||October 2022|
|Estimated Study Completion Date :||October 2022|
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.
Denosumab, one sub-cutaneous infusion, given within 2 weeks after engraftment defined as neutrophils > 0,5x10(9)/L and chimerism ≥ 10% of donor origin.
Before starting Denosumab several requirements have to be met: 1) Calcemia and Phosphatemia in the normal ranges, 2) adequate Calcium and Vitamin D intakes according to age.
Biological activity of Denosumab measured by CTX blood level, expected to last for 4 to 6 months after one infusion.
Possibility of subsequent infusions at the same dose level, every 5 to 6 months, for patient remaining on corticotherapy, provided no DLT occurred and provided CTX blood level decreased under the required threshold, after the previous infusions of Denosumab
- Maximum Tolerable Dose (MTD) [ Time Frame: 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. ]
The MTD is defined as:
- the maximum dose level at which 0 to 1 out of 6 patients experience dose-limiting toxicity (DLT) and above which 2 or more patients encounter DLT.
- or the dose of Denosumab necessary for blocking bone resorption for at least 4 months in 6 consecutive patients, if dose limiting toxicities are not observed
- Evolution of CTX (a biological marker of bone resorption) level in blood [ Time Frame: Dosage before transplantation, before beginning Denosumab, then monthly till 6 months, then at 12 months, 18 months, 24 and 36 months after starting Denosumab ]Duration of CTX level in blood on Denosumab treatment under the lower limit for age and sex, or less than 20% of the value before starting the conditioning regimen
- Evolution of P1NP (a biological marker of bone synthesis) level in blood [ Time Frame: 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 ]Level of P1NP in blood at each time point of follow-up
- Osteonecrosis (apart from jaw osteonecrosis) [ Time Frame: At 1 year, 2 years and 3 years after bone marrow transplantation ]Cumulative Incidence of osteonecrosis based on clinical diagnosis at each time point of follow-up
- Fracture [ Time Frame: At 1 year, 2 years and 3 years after bone marrow transplantation ]Cumulative Incidence of fracture based on clinical diagnosis at each time point of follow-up
- Bone Mineral Density (BMD) [ Time Frame: Before bone marrow transplantation, then 6 months, 12 months, 24 months and 36 months after starting Denosumab ]BMD is measured by a routine radiologic test named dual energy X-ray (DXA) allowing to establish the Z score of BMD
- Growth height evolution according to standardized World Health Organization growth charts for Canada [ Time Frame: Measurement every 6 months till 24 months after entering the study, then yearly till 21 years of age. ]
Evolution of growth height will be described as :
- change in percentile between percentile of height before transplantation and percentile of height along time at each time point of follow-up
- final height at the end of growth or at last follow-up
- Dose Limiting toxicity (DLT) [ Time Frame: 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. ]Grade 3 to 5 toxicities probably or definitively related to Denosumab, if MTD is reach before a blockade of bone resorption is observed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02677246
|Contact: Pierre Teira, MD||1 514 345 email@example.com|
|Contact: Marion Cortier, CRA||1 514 345 4931 ext firstname.lastname@example.org|
|St. Justine 's Hospital||Not yet recruiting|
|Montreal, Quebec, Canada, H3T1C5|
|Principal Investigator:||Pierre Teira, MD||St. Justine's Hospital|