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Disorder Related to Bone Marrow TransplantationPhase 1NCT02677246

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

A Phase 1 study testing Denosumab in people with Disorder Related to Bone Marrow Transplantation, run by St. Justine's Hospital at 1 site in Canada.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 21 years
What is being tested?
Denosumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteCanada
Study dates
Dec 2016to 4 Sep 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

Canada1 site

  • St. Justine 's Hospital

    Montreal, Quebec, H3T1C5

Other trials in Canada

About this study

Official title: Phase 1 Trial of Denosumab for Prevention of Bone Complications After Allogenic Hematopoietic Stem Cell Transplantation in Children

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.

Read the 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.

Being tested
Denosumab
Keywords
Bone marrow transplantation, Children, Bone complications, Denosumab.

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    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

Study groups in NCT02677246
Study groupRoleWhat they receive
DenosumabExperimentalPhase 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.
Receives: Drug: Denosumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerable Dose (MTD)

    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

    Measured: 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 (7)

  1. Evolution of CTX (a biological marker of bone resorption) level in blood

    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

    Measured: Dosage before transplantation, before beginning Denosumab, then monthly till 6 months, then at 12 months, 18 months, 24 and 36 months after starting Denosumab

  2. Evolution of P1NP (a biological marker of bone synthesis) level in blood

    Level of P1NP in blood at each time point of follow-up

    Measured: 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

  3. Osteonecrosis (apart from jaw osteonecrosis)

    Cumulative Incidence of osteonecrosis based on clinical diagnosis at each time point of follow-up

    Measured: At 1 year, 2 years and 3 years after bone marrow transplantation

  4. Fracture

    Cumulative Incidence of fracture based on clinical diagnosis at each time point of follow-up

    Measured: At 1 year, 2 years and 3 years after bone marrow transplantation

  5. Bone Mineral Density (BMD)

    BMD is measured by a routine radiologic test named dual energy X-ray (DXA) allowing to establish the Z score of BMD

    Measured: Before bone marrow transplantation, then 6 months, 12 months, 24 months and 36 months after starting Denosumab

  6. Growth height evolution according to standardized World Health Organization growth charts for Canada

    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

    Measured: Measurement every 6 months till 24 months after entering the study, then yearly till 21 years of age.

  7. Dose Limiting toxicity (DLT)

    Grade 3 to 5 toxicities probably or definitively related to Denosumab, if MTD is reach before a blockade of bone resorption is observed.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2016 (estimated)
  2. Study startDec 2016
  3. Primary completion4 Sep 2018
  4. Study completion4 Sep 2018

Why it stopped: lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02677246
Sponsor's protocol ID
HSJ001
Status last verified
Sep 2018
First submitted
2 Feb 2016
Last updated
6 Sep 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Denosumab in people with Disorder Related to Bone Marrow Transplantation, run by St. Justine's Hospital at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02677246.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2018.

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