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Relapsed/Refractory Multiple MyelomaPhase 2DARENCT03450057

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

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

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study was to evaluate the effects of daratumumab with dexamethasone (DaraD) in subjects with relapsed or refractory multiple myeloma and renal impairment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed/Refractory Multiple Myeloma
What is being tested?
Daratumumab with dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteGreece
Study dates
15 Feb 2018to 22 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 before performance of any study-related procedure.
  • Subject must have documented multiple myeloma as defined by the criteria below:
  • Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma.
  • AND any or more of the following myeloma defining events:
  • Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
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  • Hypercalcaemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
  • Renal insufficiency: creatinine clearance <40 mL per min or serum creatinine >177 μmol/L (>2 mg/dL)
  • Anaemia: haemoglobin value of >20 g/L below the lower limit of normal, or a haemoglobin value <100 g/L
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PETCT
  • Any one or more of the following biomarkers of malignancy:
  • Clonal bone marrow plasma cell percentage ≥60%
  • Involved:uninvolved serum free light chain ratio ≥100
  • >1 focal lesions on MRI studies
  • Prior treatment with at least two lines of treatment that included both bortezomib- and lenalidomide based regimens.
  • Documented evidence of progressive disease (PD) as defined by the modified IMWG criteria on or after the last regimen if the patient responded to previous regimens.
  • Subjects must have 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 (100 mg/L) and abnormal serum immunoglobulin kappa lambda free-light-chain ratio.
  • Renal impairment defined as eGFR < 30 ml/min/1.73 m2 (calculated with the CKD-EPI formula) or in need for dialysis. Patients who undergo intraperitoneal dialysis may also be included.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
  • 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. Females are not of reproductive potential if they have been in natural menopause for at least 24 consecutive months, or have had a hysterectomy and/or bilateral oophorectomy.
  • Women must not be breastfeeding.
  • WOCBP must 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 3 months after cessation of study treatment.
  • Males who are sexually active must always 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.
  • Male patients must not donate sperm for up to 90 days post treatment completion.
  • Female patients must not donate eggs for up to 90 days post treatment completion.
  • Azoospermic males and WOCBP who are not heterosexually active are exempt from contraceptive requirements. However, WOCBP will still undergo pregnancy testing as described in this section.

Who cannot join

  • Previous therapy with daratumumab or other anti-CD38 therapy.
  • Anti-myeloma treatment within 2 weeks prior to Cycle 1, Day 1.
  • 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.
  • Previous allogenic stem cell transplant; or Autologous Stem Cell Transplantation (ASCT) within 12 weeks before Cycle 1, Day 1.
  • Clinical signs of meningeal involvement of multiple myeloma.
  • Subject has either of the following:
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  • 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 moderate or severe persistent asthma (see Appendix 7), within 2 years from C1D1, or currently has uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
  • Clinically significant cardiac disease, including:
  • Myocardial infarction within 1 year, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
  • Uncontrolled cardiac arrhythmia (CTCAE Grade 2 or higher) (atrial fibrillation with controlled ventricular rate is allowed) or clinically significant ECG abnormalities.
  • ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
  • Any of the following:
  • Known active hepatitis A
  • Patient is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
  • Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
  • Known to be seropositive for human immunodeficiency virus (HIV).
  • Amyloidosis, or any prior or concurrent malignancy, except for the following:
  • Adequately treated basal cell or squamous cell skin cancer.
  • Any cancer (other than in-situ) from which the subject has been disease-free for 3 years prior to study entry.
  • Any of the following laboratory test results during screening:
  • Absolute neutrophil count ≤ 1.0 × 10^9/L;
  • Hemoglobin level ≤ 7.5 g/dL (≤ 4.65 mmol/L);
  • Platelet count < 75 × 10^9/L in patients in whom < 50% of bone marrow nucleated cells are plasma cells and < 50x10^9/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells;
  • Alanine aminotransferase level ≥ 2.5 times the upper limit of normal (ULN);
  • Pregnant or nursing women.

Trial locations and contacts

1 site in 1 country.

Greece1 site

  • General Hospital of Athens "Alexandra"

    Athens, Attica, 11528

Other trials in Greece

About this study

The purpose of this study was to evaluate the effects of daratumumab with dexamethasone (DaraD) in subjects with relapsed or refractory multiple myeloma and renal impairment.

Read the detailed description

This was a multicenter, single arm, open-label phase 2 study. 38 subjects were enrolled to receive daratumumab and dexamethasone. Treatment cycles had a duration of 28 days. Subjects received treatment until either disease progression, death, unacceptable toxicity or for a maximum of 30 months. Drug administration and follow-up visits occurred 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 occurred monthly and involved mainly measurements of myeloma proteins. Other assessments included bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin, and β2- microglobulin and albumin.

Being tested
Daratumumab with dexamethasone
Keywords
Multiple Myeloma, MM, Relapsed, Refractory
Medical subject headings
Multiple Myeloma, Recurrence

What participants receive

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

  • Daratumumab with dexamethasoneDrug

    Also called DaraD, Darzalex, Dara, Dex

    Daratumumab:

    Daratumumab was given at a dose of 16 mg/kg administered as an intravenous (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 received pre-infusion medications before infusions to mitigate potential infused-related reactions (IRRs).

    Dexamethasone:

    Dexamethasone was 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.

Study groups in NCT03450057
Study groupRoleWhat they receive
Single arm trial receiving daratumumab with dexamethasone (DaraD)ExperimentalDaratumumab was given at a dose of 16 mg/kg administered as an intravenous (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 was administered according to the standard recommended dose of 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.
Receives: Drug: Daratumumab with dexamethasone

What is being measured

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

  1. The Evaluation of Progression Free Survival (PFS) in Subjects With Relapsed or Refractory Multiple Myeloma and Renal Impairment Treated With Daratumumab and Dexamethasone.

    Progression free survival was defined as the time, in months, from treatment initiation (C1D1) to the date of the first documented disease progression or death due to any cause, whichever came first. Clinical deterioration was not considered progression. For patients who neither progressed nor died, the survival time was censored at the date of their last disease assessment. For patients who started a new anti-tumor treatment, survival time was censored at the date of the start of the new treatment.

    Measured: Duration from first daratumumab administration until death or last assessment, months.

Secondary outcomes (6)

  1. Overall Response Rate (ORR)

    Overall response rate was defined as the proportion of subjects who achieve a best response of PR or better using modified IMWG criteria as their best overall response.

    Measured: From first dose of Daratumumab until end of treatment, PD or death (approximately up to 30 months)

  2. Renal Response Rate (RRR)

    Renal response rate was defined as the proportion of enrolled subjects who achieve a best response of renal partial response (PRRenal) or better using the IMWG criteria.

    Measured: From first dose of Daratumumab until end of treatment, PD or death (approximately up to 30 months )

  3. Duration of Response in Patients With RI

    Duration of response was restricted to the subjects that achieve a best objective response of PR or better. It was 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).

    Measured: Assessed monthly from first dose of Daratumumab until PD or death from any cause (approximately up to 30 months)

  4. Time to Next Therapy

    Time to next therapy was 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.

    Measured: From first dose until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 30 months)

  5. Overall Survival

    Overall survival was defined as the time, in months, from the first dose of therapy to the date of death from any cause.

    Measured: Time from first dose of study treatment to death (approximately up to 30 months)

  6. To Assess the Safety and Tolerability of Daratumumab With Dexamethasone in Patients With Refractory and Relapsed Multiple Myeloma (RRMM) and Renal Impairment (RI).

    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 was 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 posted1 Mar 2018
  2. Study start15 Feb 2018
  3. Primary completion22 Mar 2021
  4. Study completion22 Mar 2021

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 and Dexamethasone
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03450057
Sponsor's protocol ID
EAE-2017/MM02
Other IDs
2017-003950-18, 2017
Acronym
DARE
Status last verified
Oct 2022
First submitted
13 Feb 2018
Last updated
29 Mar 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kastritis E, Terpos E, Symeonidis A, Labropoulou V, Delimpasi S, Mancuso K, Zamagni E, Katodritou E, Rivolti E, Kyrtsonis MC, Roussou M, Fotiou D, Theodorakakou F, Ntanasis-Stathopoulos I, Hatjiharissi E, Kanellias N, Migkou M, Cheliotis G, Manousou K, Gavriatopoulou M, Dimopoulos MA. Prospective phase 2 trial of daratumumab with dexamethasone in patients with relapsed/refractory multiple myeloma and severe renal impairment or on dialysis: The DARE study. Am J Hematol. 2023 Sep;98(9):E226-E229. doi: 10.1002/ajh.27001. Epub 2023 Jun 21. No abstract available.

    PubMed 37340832

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab with dexamethasone in people with Relapsed/Refractory 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 30 inclusion and 26 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: finished, as of the sponsor's last update on 29 Mar 2024. 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?

Yes. Results are posted in the registry (first posted 28 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

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: Duration from first daratumumab administration until death or last assessment, months.). 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 NCT03450057, which also lists 1 linked publication.

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 29 Mar 2024.

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