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Multiple MyelomaPhase 2REBUILDNCT03475628

Effects of Daratumumab Monotherapy on Bone Parameters in Patients With Relapsed and /or Refractory Multiple Myeloma

A Phase 2 study testing Daratumumab in people with Multiple Myeloma, run by Hellenic Society of Hematology at 1 site in Greece.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to evaluate the effects of daratumumab monotherapy on bone disease in patients with relapsed/refractory MM who have received at least 2 prior lines of therapy, including lenalidomide and a PI. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Daratumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
1 siteGreece
Study dates
21 Feb 2018to 20 Feb 2020
Phase
Phase 2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females at least 18 years of age.
  • Voluntary written informed consent.
  • Subject must have documented relapsed or refractory multiple myeloma as defined by the criteria below:
  • Measurable disease as defined by any of the following:
  • Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL (except for IgA subtype: ≥ 0.5 g/dL) or urine M-protein level ≥ 200 mg/24 hours; or
  • Light chain multiple myeloma for subjects without measurable disease in the serum or urine by SPEP/UPEP: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free-light-chain ratio.
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  • Prior treatment with at least two lines of therapy including lenalidomide and a PI for MM (induction followed by any planned high dose therapy or consolidation or maintenance would be considered as one regimen).
  • Documented evidence of progressive disease as defined by the IMWG 2014 on or after the last regimen.
  • Karnofsky Performance Status score of ≥ 70.
  • All of the following laboratory test results during screening:
  • Absolute neutrophil count (ANC) of ≥1.0 x 109/L.
  • Platelet count of ≥ 75 x 109/L in patients in whom <50% of bone marrow nucleated cells are plasma cells and ≥50 x 109/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells.
  • Hemoglobin value (> 7.5 g/dL).
  • Alanine aminotransferase level ≤2.5 times the upper limit of normal (ULN).
  • Adequate renal function (CrCl ≥ 30 mL/min by CKD-EPI).
  • Willingness and ability to participate in study procedures.
  • Reproductive Status:
  • Women of childbearing potential (WOCBP) must have two negative serum or urine pregnancy tests, one 10-14 days prior to start of the study drug and one within 24 hours prior to the start of study drug.
  • Women must not be breastfeeding.
  • WOCBP must agree to follow instructions for effective methods of contraception for 4 weeks before the start of treatment with study drugs, for the duration of treatment with study drugs, and for 3 months after cessation of study treatment.
  • Male patients must use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy. They must also agree to follow instructions for methods of contraception for 4 weeks before the start of treatment with study drugs, for the duration of treatment with study drugs, and for a total of 3 months post-treatment completion.

Who cannot join

  • Patient has received any of the following therapies:
  • Radiotherapy or systemic therapy within 2 weeks of baseline.
  • Prior Allogeneic hematopoietic stem cell transplantation within 12 weeks of baseline.
  • Prior Treatment with any CD38-antibody (i.e. isatuximab).
  • Clinically significant cardiac disease, including:
  • Myocardial infarction within 6 months, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
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  • Cardiac arrhythmia (CTCAE Grade 3 or higher) or clinically significant ECG abnormalities.
  • ECG showing a baseline QT interval as corrected >470 msec.
  • Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
  • Known active hepatitis A, B, or C.
  • Known HIV infection.
  • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrolment.
  • Hypersensitivity to the active substance or to any of the excipients.
  • Any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with subject's ability to give informed consent, the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
  • Pregnant or breastfeeding women.

Trial locations and contacts

1 site in 1 country.

Panayiotidis Panayiotis, Prof. contact

+30 2107211806

infohaema@eae.gr

Greece1 site, 1 recruiting
  • General Hospital of Athens "Alexandra"

    Athens, Attica, 11528

    Evangelos Terpos, Assoc Prof, +30210 3381512

    Recruiting

Other trials in Greece

About this study

Official title: A Prospective, Multicenter, Non-comparative, Open-label, Phase II Study to Evaluate the Effects of Daratumumab Monotherapy on Bone Parameters in Patients With Relapsed and /or Refractory Multiple Myeloma Who Have Received at Least 2 Prior Lines of Therapy, Including Lenalidomide and a Proteasome Inhibitor

The purpose of this study is to evaluate the effects of daratumumab monotherapy on bone disease in patients with relapsed/refractory MM who have received at least 2 prior lines of therapy, including lenalidomide and a PI.

Read the detailed description

This is a prospective, multicenter, non-comparative, open-label Phase II study. Daratumumab will be administered according to approved label. Approximately 57 subjects located in Greece will be enrolled in the study.

Patients shall receive treatment until disease progression, physician decision, unacceptable toxicity, withdrawal of consent, or death (whichever occurs first). Survival status and data of subsequent anti-myeloma treatment will be collected post-treatment.

Primary and secondary variables related to bone disease markers will be evaluated every other cycle of therapy. Disease evaluations will occur monthly and consist mainly of measurements of myeloma proteins. Other parameters may include bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin, and β2- microglobulin and albumin. Assessment of myeloma response and disease progression will be conducted in accordance with the modified IMWG response criteria

Being tested
Daratumumab
Medical subject headings
Multiple Myeloma

What participants receive

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

  • DaratumumabDrug

    Daratumumab will be given at a dose of 16 mg/kg administered as an IV infusion at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects will receive pre-infusion medications prior to Daratumumab infusion to mitigate potential IRRs and post- infusion medications after Daratumumab infusion for the prevention of delayed IRRs

Study groups in NCT03475628
Study groupRoleWhat they receive
DaratumumabExperimentalDaratumumab at a dose of 16 mg/kg administered as an IV infusion at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter.
Receives: Drug: Daratumumab

What is being measured

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

  1. changes in bone resorption marker, C-telopeptide of collagen type 1 (CTX), after 4 months of daratumumab monotherapy

    The evaluation of the changes in bone resorption marker after 4 months of daratumumab monotherapy. CTX (measured in pg/ml) will be evaluated at baseline and then every 2 months of therapy.

    Measured: assessed on baseline and after 4 months from initiation of daratumumab monotherapy

  2. changes in bone resorption marker, namely, tartrate-resistant acid phosphatase-5b (TRACP-5b) after 4 months of daratumumab monotherapy

    The evaluation of the changes in bone resorption marker after 4 months of daratumumab monotherapy. TRACP-5b (measured in mU/dL) will be evaluated at baseline and then every 2 months of therapy

    Measured: assessed on baseline and after 4 months from initiation of daratumumab monotherapy

Secondary outcomes (20)
  1. Changes in bone formation marker, bALP.

    Change from baseline in bone formation marker bALP (measured in U/L) after 4, 8 and 12 months of daratumumab monotherapy (or at the end of therapy)

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  2. Changes in bone formation marker, OC.

    Change from baseline in bone formation marker OC (measured in ng/ml) after 4, 8 and 12 months of daratumumab monotherapy (or at the end of therapy)

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  3. Changes in bone formation marker, PINP.

    Change from baseline in bone formation marker PINP (measured in ng/ml) after 4, 8 and 12 months of daratumumab monotherapy (or at the end of therapy)

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  4. Changes in bone resorption marker, CTX.

    Change from baseline in bone resorption marker CTX (measured in pg/ml) after 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to12 months of daratumumab monotherapy or at end of treatment

  5. Changes in bone resorption marker, TRACP-5b.

    Change from baseline in bone resorption marker TRACP-5b (measured in mU/dL) after 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to12 months of daratumumab monotherapy or at end of treatment

  6. Changes in bone marker RANKL

    Change from baseline in RANKL (measured in pg/ml) after 4, 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  7. Changes in bone marker ratio,RANKL/OPG ratio.

    Change from baseline in RANKL/OPG ratio after 4, 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  8. Changes in bone marker CCL3

    Change from baseline in CCL3 (measured in pg/ml) after 4, 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  9. Changes in bone marker Dkk1

    Change from baseline in Dkk1 (measured in ng/ml) after 4, 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  10. Changes in bone marker SOST

    Change from baseline in SOST (measured in pmol/L) after 4, 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  11. Changes in bone marker activin-A

    Change from baseline in activin-A (measured in μg/L) after 4, 8 and 12 months of daratumumab monotherapy

    Measured: from baseline up to 12 months of daratumumab monotherapy or at end of treatment

  12. Change in Bone Mineral Density (BMD) of lumbar spine

    Change in Bone Mineral Density (BMD) of lumbar spine measured by DXA after 6 and 12 months of daratumumab monotherapy

    Measured: measured at baseline and after 6 and 12 months after initiation of daratumumab monotherapy

  13. Immunomodulatory effects of daratumumab on T cells by comprehensive molecular and phenotypic studies and correlations with bone markers

    Immunomodulatory effects of daratumumab on T cells by comprehensive molecular and phenotypic studies and correlations with bone markers

    Measured: : measured at baseline and after 3 and 6 months after initiation of daratumumab monotherapy

  14. Progression free survival (PFS)

    Progression free survival is defined as the time, in months, from recruitment to the date of the first documented PD or death due to any cause, whichever comes first. PD will be assessed by the investigator based on the analysis of serum and urine protein electrophoresis (sPEP and uPEP), serum free light chain protein (sFLC), Corrected serum calcium assessment, imaging and bone marrow assessments as per modified IMWG guidelines.

    Measured: from recruitment to the date of the first documented PD or death due to any cause, whichever comes first (approximately up to 2 years).

  15. Overall survival

    Overall survival is defined as the time, in months

    Measured: Time from first dose of study treatment to death (approximately up to 2 years)

  16. Time to next treatment

    Time to next therapy will be defined as the time, in months.

    Measured: From first dose until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 2 years)

  17. Spinal cord compression (Skeletal surveys-Skeletal related events)

    Spinal cord compression will be evaluated in terms of number (and percentage) of patients with events and number of events per patient

    Measured: From baseline to 24 months (up to 2 years)

  18. The incidence of pathological fractures (Skeletal surveys-Skeletal related events)

    The incidence of pathological fractures will be evaluated in terms of number (and percentage) of patients with events and number of events per patient

    Measured: From baseline to 24 months (up to 2 years)

  19. Need for radiotherapy or surgery to the bones (Skeletal surveys-Skeletal related events)

    Need for radiotherapy or surgery to the bones will be evaluated in terms of number (and percentage) of patients with events and number of events per patient

    Measured: From baseline to 24 months (up to 2 years)

  20. Safety (adverse events)

    The incidence of Adverse Events will be assessed according to the common Terminology Criteria for Adverse Events.

    Measured: Continuously throughout the study, starting from informed consent until 30 days after last study treatment (approximately up to 30 months)

Timeline

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

  1. First posted23 Mar 2018
  2. Study start21 Feb 2018
  3. Primary completion20 Jun 2019 (estimated)
  4. Study completion20 Feb 2020 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single arm: Daratumumab
Masking
None (open label)
Enrolment
57 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03475628
Sponsor's protocol ID
EAE-2017/MM01
Acronym
REBUILD
Status last verified
Mar 2018
First submitted
22 Feb 2018
Last updated
23 Mar 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab in people with Multiple Myeloma, run by Hellenic Society of Hematology at 1 site in Greece.

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 21 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 23 Mar 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 Greece. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Panayiotidis Panayiotis, Prof. (+30 2107211806, infohaema@eae.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

changes in bone resorption marker, C-telopeptide of collagen type 1 (CTX), after 4 months of daratumumab monotherapy (time frame: assessed on baseline and after 4 months from initiation of daratumumab monotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 23 Mar 2018.

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