AzTrials
AzTrials

Multiple MyelomaPhase 2IFM2014-04NCT02626481

Study of Daratumumab in Combination With Dexamethasone in Resistant or Refractory Multiple Myeloma

A Phase 2 study testing Daratumumab and Dexamethasone in people with Multiple Myeloma, run by University Hospital, Lille at 41 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

This study is a Multicentre, Open-label, Phase II study of Daratumumab and Dexamethasone in MM patients. Eligible patients must have a symptomatic RRMM with a measurable disease, resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide. 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 and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
41 sitesin 2 countries
Study dates
28 Dec 2015to 9 Mar 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

  • Must be able to understand and voluntarily sign an informed consent form
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Age ≥18 years
  • Life expectancy > 6 months
  • Patients must have relapsed myeloma, and previously treated with Bortezomib, Lenalidomide, and Pomalidomide treatment, and being resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide treatment, defined as follows:
  • 5.1. Any number of prior therapies 5.2. Patients must have Progressive Disease as defined by the IMWG as one of the following (Kyle, 2009):
Show all 41Show fewer
  • Increase of 25% from lowest response value in any one or more of the following:
  • Serum M-component (absolute increase must be ≥ 0.5 g/100 ml)b and/or Urine M-component (absolute increase must be ≥ 200 mg per 24 h) and/or
  • Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved
  • FLC levels (absolute increase must be > 10 mg/l). Bone marrow plasma cell percentage (absolute % must be ≥ 10%)
  • Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
  • Development of hypercalcemia (corrected serum calcium > 11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder 5.3. Patients must have undergone prior treatment with Bortezomib and Lenalidomide and Pomalidomide:
  • They must have received at least two cycles of therapy
  • Either at diagnosis or relapse
  • Either in separate regimens or within the same regimen
  • The line of treatment with Bortezomib and/or Lenalidomide and/or Pomalidomide does not need to be the very last line of prior therapy
  • Patients must have a clearly detectable and quantifiable monoclonal M-component value:
  • IgG (serum M-component > 10g/l) IgA (serum M-component >5g/l) IgD (serum M-component > 0.5g/l) Light chain (serum M-component >1g/l or Bence Jones > 200mg/24H) In patients without measurable serum and urine M-protein levels when the absolute serum FreeLight chain (sFLC) is ≥100 mg/l and an abnormal sFLC K/λ ratio (<0.26 and >1.65) is found (Dispenzieri, 2008).
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Adequate bone marrow function within 5 days prior to 1st drug intake (cycle1, day 1, C1D1), without transfusion nor growth factor support within 5 days prior to 1st drug intake , defined as:
  • Absolute neutrophils ≥ 1000/mm3 Platelets ≥ 50000/mm3 Haemoglobin ≥ 8.5g/dl
  • Adequate organ function defined as:
  • Serum creatinine clearance (Cockcroft-Gault formula) ≥30 ml/min Serum SGOT or SGPT < 3.0 X upper limit of normal (ULN) Serum total bilirubin < 2.0 mg/dL
  • Wash out period of at least 2 weeks from previous antitumor therapy or any investigational treatment or 5 half-lives from previous antibodies.
  • Women who are partners of men and of childbearing potential must be practicing one of the following methods of birth control: subcutaneous hormonal implant, levonorgestrel releasing intra-uterine system, medroxyprogesterone acetate depot, tubal sterilization, ovulation inhibitory progesterone only pills, or sexual intercourse with a vasectomized male partner (vasectomy must be confirmed by 2 negative semen analyses). Or women will commit to absolute and continuous abstinence confirmed to her physician on a monthly basis. Childbearing potential*. Contraception will start during therapy including dose interruptions, for 4 months after discontinuation of Daratumumab.
  • Criteria for women of childbearing potential :
  • This protocol defines a female of childbearing potential as a sexually mature woman who:
  • has not undergone a hysterectomy or bilateral oophorectomy or
  • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) 12. A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 28 days prior to dosing and the second within 48 hours prior to dosing, and remain on a highly effective method of birth control. The two methods of reliable contraception must include one highly effective method and one additional effective (barrier) method. FCBP must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:
  • Highly effective methods:
  • Intrauterine device (IUD)
  • Hormonal (birth control pills, injections, implants)
  • Tubal ligation
  • Partner's vasectomy
  • Additional effective methods:
  • Male condom
  • Diaphragm
  • Cervical Cap 13. Serum (urine in the case where serum is not possible in a timely manner) pregnancy test to be performed for all women of childbearing potential regularly during the study,. In addition, a pregnancy test may be done at any time during the study at the discretion of the investigator if a subject misses a period or has unusual menstrual bleeding.
  • 14. A woman of childbearing potential must remain on a highly effective method of birth control. Contraception must begin 4 weeks before initiating treatment with Daratumumab, during therapy, during dose interruptions and continuing for 4 months following discontinuation of Daratumumab. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.
  • 15. A man who has not had a vasectomy and who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control eg, condom with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study, for 4 months following discontinuation of Daratumumab. The exception to this restriction is that if the subject's female partner is surgically sterile, a second method of birth control is not required.
  • 16. Subjects affiliated with an appropriate social security system.

Who cannot join

  • Target disease exceptions:
  • Solitary bone/solitary extramedullary plasmocytoma
  • Patients with non-secretory MM and non-measurable MM
  • Evidence of central nervous system (CNS) involvement
  • Medical history and Concurrent disease:
  • o Subjects with prior (≤ 5 years) or concurrent invasive malignancies except the following: Adequately treated basal cell or squamous cell skin cancer Incidental finding of low grade (Gleason 3+3 or less) prostate cancer Any cancer from which the subject has been disease free for at least 3 years.
Show all 24Show fewer
  • Subject with known/underlying medical conditions that, in the investigator's opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes or uncontrolled coronary artery disease)
  • Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including:
  • NYHA functional classification III or IV congestive heart failure LVEF ( Left Ventricular Ejection Fraction) ≥45% Uncontrolled angina, hypertension or arrhythmia Myocardial infarction in the past 6 months
  • Subjects with grade 2 or greater peripheral neuropathy (as per NCI-CTCAEv4.0)
  • Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen.
  • Known positive for HIV or active hepatitis B or C.
  • Subjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
  • Subjects with known 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 patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
  • Subjects with a history of moderate or severe persistent asthma within the past 2 years (see appendix), or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
  • Physical and laboratory test findings:
  • Patients on dialysis or with a Creatinine clearance < 30mL/min
  • SGOT or SGPT >3ULN
  • Prohibited prior therapies
  • Prior local irradiation within two weeks before first dose
  • Previous anti-CD38 therapy.
  • Allergies and Adverse Drug Reaction:
  • o Hypersensitivity to Dexamethasone that would prohibit treatment with study therapy
  • Refusal to consent or protected by a legal regime (guardianship, trusteeship)

Trial locations and contacts

41 sites in 2 countries.

41 sites in 2 countries

France37 sites

  • CHRU - Hôpital du Bocage (Amiens)

    Amiens, 49033

  • CHRU-Hôpital Sud d'Amiens

    Amiens, 80054

  • Hôpital Avicenne

    Bobigny, 93009

  • Polyclinique Bordeaux Nord Aquitaine

    Bordeaux, 33300

  • Hôpital du Haut Lévêque Centre François Magendie

    Bordeaux, 33604

  • Clinique - ICH CHU de Brest Hôpital Morvan

    Brest, 29609

  • CHRU Côte de Nacre

    Caen, 14033

  • Centre Hospitalier William Morey

    Chalon-sur-Saône, 71100

  • Hôpital d'instruction des armées Percy

    Clamart, 92141

  • Hématologie Clinique CHU DIJON

    Dijon, 21000

  • Centre Hospitalier Général

    Dunkirk, 59 385

  • CHRU, Hôpital A.Michallon

    Grenoble, 38043

  • Médecine interne Centre hospitalier départemental

    La Roche-sur-Yon, 85025

  • Service d'Hématologie CHV André Mignot

    Le Chesnay, 78157

  • CHRU , Hôpital Claude Huriez

    Lille

  • Sce Hématologie Thérapie Cellulaire CHU Limoges

    Limoges, 87000

  • Institut Paoli Calmette

    Marseille, 13273

  • Hopital J Monod Sce Rhumato Nord

    Montivilliers, 76290

  • Service Hématologie CHRU Montpellier

    Montpellier, 34090

  • Hopital E Muller

    Mulhouse, 68100

  • Maladies du sang CHRU Hôtel Dieu

    Nantes, 44035

  • URC/CIC Paris Descartes Necker-Cochin

    Paris, 75015

  • Curie Institut

    Paris, 75248

  • Hôpital Saint-Louis

    Paris, 75475

  • CHU - Hôpital St Antoine

    Paris, 75571

  • Unité de Recherche Clinique - CH Périgueux

    Périgueux, 24019

  • Centre Hospitalier Lyon sud

    Pierre-Bénite, 69495

  • CHU de la milétrie

    Poitiers, 86000

  • Hôpital R.Debré

    Reims, 51032

  • Hôpital de Pontchaillou

    Rennes, 35033

  • Service Hématologie Centre Hospitalier Yves le Foll

    Saint-Brieuc, 22000

  • Service d'Hématologie Clinique Institut de Cancérologie Lucien Neuwirth

    Saint-Priest-en-Jarez, 42270

  • Département d'Hématologie et Oncologie Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67091

  • Hématologie CHRU IUCT Oncopole

    Toulouse, 31100

  • Onco-hématologie CHRU Hôpital Bretonneau

    Tours, 37044

  • Hôpitaux de Brabois

    Vandœuvre-lès-Nancy, 54511

  • service hématologie CH Bretagne Atlantique

    Vannes, 56017

Other trials in France

Belgium4 sites

  • AZ ST Jan hematology department

    Bruges, 8000

  • Hematologie Laarbeeklaan

    Brussels, 101 - 1090

  • Jules Bordet Institute

    Brussels, B - 1000

  • CHU Dinant Godinne | UCL Namur asbl

    Yvoir, 1 - 5530

Other trials in Belgium

About this study

Official title: A Multicenter Open Label Phase II Study of Daratumumab in Combination With Dexamethasone in Multiple Myeloma Resistant or Refractory to Bortezomib and Lenalidomide and Pomalidomide - an IFM 2014-04 Study

This study is a Multicentre, Open-label, Phase II study of Daratumumab and Dexamethasone in MM patients. Eligible patients must have a symptomatic RRMM with a measurable disease, resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide.

There is no dose escalation phase, as the MAxiamal Tolerated Dose (MTD) and drug scheduling have already been determined in previous phase 1-2 dose escalation studies. There is no randomization.

Read the detailed description

Multiple myeloma (MM) is the second most common haematological malignancy (after non-Hodgkin's lymphoma), representing 1% of all cancers and 2% of all cancer deaths. Despite the increased efficacy of first-line agents, the majority of patients will eventually relapse and become resistant to all classes of available therapies. With over 15,000 deaths from MM expected in 2014 in the United states of America (USA) alone, there remains a need for novel therapies for the treatment of refractory MM that can improve outcome Daratumumab is an IgG1ĸ human mAb that specifically recognizes the CD38 epitope. Daratumumab binds to the C-terminus of CD38. It is produced in a recombinant Chinese Hamster Ovary (CHO) cell line. Standard mammalian cell culture and purification technologies are employed in the manufacture of Daratumumab. Daratumumab targets directly the tumour cells by selectively binding to CD38 receptors, present in high levels on malignant plasma cells in multiple myeloma. While binding of Daratumumab antibody to CD38 in vitro has some effect on enzyme activity (inhibiting cyclase and stimulating hydrolase activity), the main effect of Daratumumab antibody binding to CD38+ myeloma cell lines is lysis and cell death through complement dependent cytotoxicity (CDC), through antibody dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cell phagocytosis (ADCP), or by direct apoptosis following crosslinking of the antibody molecules. These mechanisms are likely to be involved in Daratumumab activity in vivo, although the primary mechanism of action in patients is not fully elucidated. Importantly, Daratumumab-induced ADCC and CDC was not affected by the presence of bone marrow stromal cells, indicating that Daratumumab can effectively kill MM tumour cells in a tumour-preserving bone marrow microenvironment. In vivo, Daratumumab was highly active and interrupted xenograft tumour growth at low dosing. Daratumumab has demonstrated activity in myeloma as a single agent in small phase I/II studies and in combination with Lenalidomide and Dexamethasone where it enhanced the potency of other MM drugs such as Lenalidomide offering an interesting alternative to chemotherapy in myeloma.

Keywords
Multiple Myeloma, Cancer, refractory, daratumumab
Medical subject headings
Multiple Myeloma, Neoplasms

What participants receive

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

  • DaratumumabDrug

    Also called Experimental Arm

    patients treated with Daratumumab (16 mg/kg) and Dexamethasone (40 or 20 mg regarding age of patient)

  • DexamethasoneDrug

    Also called Experimental Arm

    patients treated with Dexamethasone (40 or 20 mg regarding age of patient)

Study groups in NCT02626481
Study groupRoleWhat they receive
Daratumumab + DexamethasoneExperimentalpatients treated with Daratumumab (16 mg/kg) and Dexamethasone (40 or 20 mg regarding age of patient)
Receives: Drug: Daratumumab; Drug: Dexamethasone

What is being measured

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

  1. Number of best Overall Response using the IMWG response criteria

    best Overall Response Rate (ORR, PR or better) using the IMWG response criteria.

    Measured: 60 months

Secondary outcomes (3)

  1. Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

    Assess safety by type, frequency, severity, relationship of adverse events to study treatment and changes in vital signs, physical exams. Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and laboratory abnormalities using National Cancer Institute (NCI) common toxicity criteria (CCTAE V4).

    Measured: 60 months

  2. Number of patients who reach Very Good Partial Response and Complete using IMWG response criteria

    Response rate (VGPR and CR) to Daratumumab and Dexamethasone in the study population using IMWG response criteria.

    Measured: 60 months

  3. Rate of Overall Survival (OS)

    Determine the OS (from the date of inclusion to last date of follow-up) of patients treated with Daratumumab+ Dexamethasone.

    Measured: 60 months

Timeline

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

  1. First posted10 Dec 2015 (estimated)
  2. Study start28 Dec 2015
  3. Primary completion9 Mar 2020
  4. Study completion9 Mar 2020

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
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02626481
Sponsor's protocol ID
2015_29
Other IDs
2015-002221-19, 2015
Acronym
IFM2014-04
Status last verified
Mar 2021
First submitted
16 Nov 2015
Last updated
7 Apr 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Boyle EM, Leleu X, Petillon MO, Karlin L, Doyen C, Demarquette H, Royer B, Macro M, Moreau P, Fostier K, Marie-Lorraine C, Zarnitsky C, Perrot A, Herbaux C, Poulain S, Manier S, Beauvais D, Walker BA, Wardell CP, Vincent L, Frenzel L, Caillon H, Susanna S, Dejoie T, Avet-Loiseau H, Mohty M, Facon T; IFM2014-04 investigators. Daratumumab and dexamethasone is safe and effective for triple refractory myeloma patients: final results of the IFM 2014-04 (Etoile du Nord) trial. Br J Haematol. 2019 Nov;187(3):319-327. doi: 10.1111/bjh.16059. Epub 2019 Jun 19.

    PubMed 31218679

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab and Dexamethasone in people with Multiple Myeloma, run by University Hospital, Lille at 41 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 41 inclusion and 24 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 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in France, Belgium. 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?

Number of best Overall Response using the IMWG response criteria (time frame: 60 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 NCT02626481, 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 7 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in