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Multiple MyelomaPhase 2GMMG-DANTENCT02977494

Daratumumab in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma and Severe Renal Impairment

A Phase 2 study testing Daratumumab, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Universitätsklinikum Hamburg-Eppendorf at 10 sites in 2 countries.

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

Myeloma patients with renal impairment need a rapid and effective reduction of tumor burden to enable renal recovery, which is correlated with prognosis of the patients. However, effective combination regimens are often hampered by necessary dose reductions or increased toxicity in renally impaired patients. 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, Bortezomib and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
10 sitesin 2 countries
Study dates
Jun 2016to Jun 2021
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

  • Subjects must be at least 18 years of age
  • Written informed consent
  • Subjects must have had documented multiple myeloma requiring treatment as defined by the criteria below:
  • Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma at some point in their disease history requiring treatment according diagnostic criteria (IMWG updated criteria 2014, Rajkumar et al. 2014) see appendix I With measurable disease at screening (serum M-protein > 500 mg/dl or urine M-protein > 200 mg/24h, in case of oligosecretory MM serum free light chain > 10 mg/dl and abnormal kappa/lambda free light chain ratio)
  • GFR < 30 ml/min and /or subjects undergoing hemodialysis
  • Subject must have received at least 1 prior treatment line
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  • Subjects must have documented evidence of progressive disease after the last treatment line
  • ECOG performance status 0-3 (ECOG 3 is only allowed if due to myeloma disease)
  • Subjects must have certain pretreatment laboratory values meeting the following criteria during the Screening Phase:
  • Hemoglobin ≥7.5 g/dl (4,66 mmol/L; prior red blood cells (RBC) transfusion or recombinant human erythropoietin use is permitted).
  • Absolute neutrophil count ≥ 1.0 x109/L (granulocyte colony stimulating factor (GCSF) use is permitted);
  • Platelet count more or equal 70 x109/L for subjects in whom ˂ 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count ˃ 50 x 109/L (transfusions are not permitted to achieve this minimum platelet count ),
  • Aspartate aminotransferase (AST) ≤ 2,5 x upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) ≤ 2,5 x ULN
  • Total bilirubin ≤ 2.0 x ULN ,except in subjects with congenital bilirubinemia, such as Gilbert syndrome (direct bilirubin ≤ 2.0 x ULN
  • Corrected serum calcium ≤ 14 mg/dl (≤3,5mmol/L); or free ionized calcium ˂ 6,5 mg/dL(˂1,6 mmol/L)
  • Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device [IUD], hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.
  • A woman of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to treatment start.

Who cannot join

  • Subject has received prior Daratumumab or other Anti-CD38 antibodies (previous treatment with Elotuzumab is allowed)
  • Evidence of intolerance to bortezomib or known allergies, hypersensitivity or intolerance to monoclonal antibodies
  • Subject has received anti-myeloma treatment within 2 weeks of Cycle 1, day 1. The only exception is emergency use of a short course of corticosteroids (equivalent of Dexamethasone 40 mg/day for a maximum of 4 days) before treatment.
  • Active graft-versus host disease under immunosuppressive treatment
  • Subject is a woman who is pregnant or breastfeeding
  • Prior invasive malignancy within 5 years before trial inclusion
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  • Active, uncontrolled infection.
  • Subject has peripheral neuropathy ≥ 3 or neuropathic pain Grade 2 or higher
  • Subject has either of the following:
  • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is only required for subjects suspected of having COPD
  • Known moderate or severe persistent asthma, 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).
  • Subject has clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry, unstable angina, cardiac insufficiency New York Heart Association (NYHA) Class III-IV or uncontrolled arrhythmia
  • Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significant is defined by presence of serum M-protein ˂ 3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less (Kyle et al. 2003). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment and organ damage (Kyle et al., 2003, 2007).
  • Subject has a diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
  • Subject has had radiation therapy within 14 days of treatment
  • Subject has had plasmapheresis within 14 days of treatment. Screening laboratory values have to be performed after end of plasmapheresis.
  • Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis B surface and core antigen (anti HBs and anti HBc respectively), or hepatitis C (anti-HCV antibody positive or HCV RNA quantitation positive).
  • Subject has had major surgery within 2 weeks before treatment und has not fully recovered from surgery, or has surgery panned during the time the subject is expected to participate in the study.
  • Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs
  • Subject has any concurrent medical or psychiatric condition or disease (eg. active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for the participating in this study.
  • Subject has known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products.
  • Subject is known or suspected of not being able to comply with the study protocol (eg. because of alcoholism, drug dependency, or psychological disorder). Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit or confound the protocol-specified assessments. Subject is taking any prohibited medication

Trial locations and contacts

10 sites in 2 countries.

10 sites in 2 countries

Germany9 sites

  • Charité Universitätsmedizin BerlinCampus Benjamin Franklin

    Berlin

  • Vivantes Klinikum Neukölln

    Berlin

  • Klinikum Chemnitz GmbH

    Chemnitz

  • Katholische Karl-Leisner Klinikum Goch

    Goch

  • Asklepios Klinik Altona

    Hamburg

  • University Hospital Hamburg Eppendorf

    Hamburg

  • Universitätsklinikum Heidelberg

    Heidelberg

  • Univerisity Hospital Muenster

    Münster

  • University Hospital

    Tübingen

Other trials in Germany

Greece1 site

  • Alexandra Hopsital

    Athens

Other trials in Greece

About this study

Official title: Daratumumab in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma and Severe Renal Impairment Including Subjects Undergoing Hemodialysis: A Phase 2, Open-label, Multicenter Trial

Myeloma patients with renal impairment need a rapid and effective reduction of tumor burden to enable renal recovery, which is correlated with prognosis of the patients. However, effective combination regimens are often hampered by necessary dose reductions or increased toxicity in renally impaired patients. The well known positive effects on renal impairment by Bortezomib combined with Daratumumab, which, as all monoclonal Antibody, is not renally excreted or metabolized and as so far known should not add significant toxicity but efficacy, makes the proposed combination of Daratumumab, Bortezomib and Dexamethasone highly attractive for renally impaired MM patients.

In the current clinical trials with Daratumumab patients with renal function impairment (GFR ≤ 20 ml/min) were so far excluded. Consequently questions about efficacy, safety and pharmacokinetics of Daratumumab in combination with Bortezomib and Dexamethasone in patients with relapsed and refractory MM and severe renal impairment are still unanswered. This trial will answer these questions for a patient group, who has still an unmet need for novel and effective treatment options

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

    Also called Darzalex

    Daratumumab (JNJ-54767414) is a novel human IgG1monoclonal Antibody (mAb) that binds with high affinity to a unique epitope on CD38

  • BortezomibDrug

    Also called Velcade

  • DexamethasoneDrug

    Also called Fortecortin

Study groups in NCT02977494
Study groupRoleWhat they receive
Daratumumab BortezomibExperimentalNot described
Receives: Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone

What is being measured

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

  1. Evaluate the efficacy (overall response rate, ORR according to IMWG recommendations) of the combination of daratumumab, bortezomib and dexamethasone in subjects with relapsed and refractory MM and impaired renal function

    Measured: two years

Timeline

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

  1. First posted30 Nov 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionJun 2021
  4. Study completionJun 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
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02977494
Sponsor's protocol ID
2016-000433-51
Other IDs
2016
Acronym
GMMG-DANTE
Status last verified
May 2022
First submitted
17 Nov 2016
Last updated
31 May 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Universitätsklinikum Hamburg-Eppendorf at 10 sites in 2 countries.

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 18 inclusion and 22 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 31 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany, 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Evaluate the efficacy (overall response rate, ORR according to IMWG recommendations) of the combination of daratumumab, bortezomib and dexamethasone in subjects with relapsed and refractory MM and impaired renal function (time frame: two years). 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 NCT02977494.

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 31 May 2022.

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