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Efficacy of Daratumumab in Patients With Relapsed/Refractory Myeloma With Renal Impairment

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ClinicalTrials.gov Identifier: NCT03450057
Recruitment Status : Recruiting
First Posted : March 1, 2018
Last Update Posted : March 1, 2018
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Hellenic Society of Hematology

Brief Summary:
This study will evaluate the effects of Daratumumab with dexamethasone in subjects with relapsed or refractory multiple myeloma and renal impairment.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Phase 2

Detailed Description:
This is a multicenter, single arm, open-label phase 2 study. Approximately 38 subjects will be enrolled to receive daratumumab + dexamethasone. Treatment cycles have duration of 28 days. Subjects will receive treatment until disease progression, death, unacceptable toxicity or for a maximum of 30 months. Drug administration and follow-up visits will occur more frequently for early cycles (weekly for the first 8 weeks, every two weeks for weeks 9-24 and then every 4 weeks). Disease evaluations will occur monthly and will involve mainly measurements of myeloma proteins. Other assessments may include bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin, and β2- microglobulin and albumin.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm: Daratumumab + Dexamethasone
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Daratumumab in Patients With Relapsed/Refractory Myeloma With Renal Impairment
Actual Study Start Date : February 15, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
Experimental: Daratumumab + Dexamethasone

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.

Dexamethasone 40 mg (20 mg for patients>75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle

Drug: Daratumumab

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 before infusions to mitigate potential IRRs

Drug: Dexamethasone

Dexamethasone will be administered at 40 mg (20 mg for patients >75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle





Primary Outcome Measures :
  1. The evaluation of progression free survival (PFS) in subjects with relapsed or refractory multiple myeloma and renal impairment treated with daratumumab and dexamethasone [ Time Frame: Assessed monthly until disease progression (PD) or death whichever occurs first (approximately up to 30 months) ]
    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.


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: From first dose of Daratumumab until end of treatment, PD or death (approximately up to 30 months ]
    Overall response rate is defined as the proportion of subjects who achieve a best response of PR or better using modified IMWG criteria as their best overall response.

  2. Renal response rate (RRR) [ Time Frame: From first dose of Daratumumab until end of treatment, PD or death (approximately up to 30 months ) ]
    Renal response rate is defined as the proportion of enrolled subjects who achieve a best response of renal partial response (PRRenal) or better using the IMWG criteria

  3. Duration of response in patients with RI [ Time Frame: Assessed monthly from first dose of Daratumumab until PD or death from any cause (approximately up to 30 months) ]
    Duration of response will be restricted to the subjects that achieve a best objective response of PR or better. It is measured from the time, in months, that the criteria for objective response are first met until the date of a progression event (according to the primary definition of PFS)

  4. Time to next therapy [ Time Frame: From first dose until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 30 months) ]
    Time to next therapy will be defined as the time, in months, from Cycle 1 Day 1 to the date to next anti-neoplastic therapy or death from any cause, whichever comes first

  5. Overall survival [ Time Frame: Time from first dose of study treatment to death (approximately up to 30 months) ]
    Overall survival is defined as the time, in months, from the first dose of therapy to the date of death from any cause

  6. The incidence of Adverse Events and Treatment Emergent Adverse Events in patients with refractory and relapsed multiple myeloma and renal impairment treated with Daratumumab with dexamethasone. [ Time Frame: Continuously throughout the study, starting from informed consent until 30 days after last study treatment (approximately up to 30 months) ]
    The incidence of Adverse Events will be assessed according to the common Terminology Criteria for Adverse Events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females at least 18 years of age.
  2. Voluntary written informed consent before performance of any study-related procedure.
  3. Subject must have documented relapsed or refractory multiple myeloma as defined by the criteria below:

    1. Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma.
    2. 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: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free-light-chain ratio.
  4. Prior treatment with at least two lines of treatment that included both bortezomib- and lenalidomide-based regimens.
  5. Documented evidence of progressive disease (PD) as defined by the IMWG 2014 on or after the last regimen if the patient responded to previous regimens.
  6. Renal impairment defined as eGFR < 30 ml/min/1.72 m2 (calculated with the CKD-EPI formula) or in need for dialysis
  7. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
  8. Willingness and ability to participate in study procedures.
  9. Reproductive Status

Exclusion Criteria:

  1. Previous therapy with Daratumumab or other anti-CD38 therapy.
  2. Anti-myeloma treatment within 2 weeks prior to Cycle 1, Day 1.
  3. Cumulative dose of corticosteroids greater than or equal to the equivalent of 140mg prednisone for ≥4 days or a dose of corticosteroids greater than or equal to the equivalent of 40 mg/day of dexamethasone for ≥4 days within the 2-week period prior to Cycle 1, Day 1.
  4. Previous allogenic stem cell transplant; or Autologous Stem Cell Transplantation (ASCT) within 12 weeks before Cycle 1, Day 1.
  5. Clinical signs of meningeal involvement of multiple myeloma.
  6. Chronic obstructive pulmonary disease (COPD), persistent asthma, or a history of asthma within 5 years.
  7. Clinically significant cardiac disease, including:

    1. Myocardial infarction within 1 year, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
    2. Cardiac arrhythmia (CTCAE Grade 2 or higher) or clinically significant ECG abnormalities.
    3. ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
  8. Known active hepatitis B, or C.
  9. Known HIV infection.
  10. Prior or concurrent malignancy, except for the following:

    1. Adequately treated basal cell or squamous cell skin cancer.
    2. Any cancer (other than in-situ) from which the subject has been disease-free for 3 years prior to study entry.
  11. Any of the following laboratory test results during Screening:

    1. Absolute neutrophil count ≤1.0 × 109/L;
    2. Hemoglobin level ≤7.5 g/dL (≤4.65 mmol/L);
    3. Platelet count <75 × 109/L in patients in whom <50% of bone marrow nucleated cells are plasma cells and <50x109/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells;
    4. Alanine aminotransferase level ≥2.5 times the upper limit of normal (ULN);
  12. Pregnant or nursing women

Information from the National Library of Medicine

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): NCT03450057


Contacts
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Contact: Panayiotidis Panayiotis, Prof. +30 2107211806 infohaema@eae.gr

Locations
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Greece
General Hospital of Athens "Alexandra" Recruiting
Athens, Attica, Greece, 11528
Contact: Efstathios Kastritis, Assoc Prof    +30210 3381512      
Sponsors and Collaborators
Hellenic Society of Hematology
Janssen Pharmaceuticals
Investigators
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Principal Investigator: Efstathios Kastritis, Assoc Prof Department of Clinical therapeutics, National and Kapodistrian University of Athens, School of medicine, Athens, Greece

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Responsible Party: Hellenic Society of Hematology
ClinicalTrials.gov Identifier: NCT03450057     History of Changes
Other Study ID Numbers: EAE-2017/MM02
First Posted: March 1, 2018    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Daratumumab
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents