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

NCT03475628 | Unknown Phase 2

• 1 other identifier: EAE-2017/MM01
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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

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

Secondary Outcomes (20)

• Changes in bone formation marker, bALP.

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

• Changes in bone formation marker, OC.

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

• Changes in bone formation marker, PINP.

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

• Changes in bone resorption marker, CTX.

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

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

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

Study Arms (1)

Daratumumab

EXPERIMENTAL

Daratumumab 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.

Drug: Daratumumab

Interventions

Daratumumab DRUG

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

Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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.
• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

General Hospital of Athens "Alexandra"

Athens, Attica, 11528, Greece

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Evangelos Terpos, Assoc Prof

  Department of Clinical therapeutics, National and Kapodistrian University of Athens, School of medicine, Athens, Greece

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Panayiotidis Panayiotis, Prof.

CONTACT

+30 2107211806; infohaema@eae.gr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm: Daratumumab

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: March 23, 2018
• Study Start: February 21, 2018
• Primary Completion: June 20, 2019
• Study Completion: February 20, 2020
• Last Updated: March 23, 2018

Record last verified: 2018-03

Locations

GR (1)