Multiple MyelomaPhase 2GMMG-DADANCT04656951
Daratumumab for First Line Treatment of Transplant-ineligible Myeloma Patients Followed by Daratumumab Re-treatment at First Relapse
A Phase 2 study testing Daratumumab in people with Multiple Myeloma, run by University of Cologne at 1 site in Germany.
Trial summary
Daratumumab for first line treatment of transplant-ineligible myeloma patients followed by daratumumab re-treatment at first relapse (GMMG-DADA) 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jun 2021to Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Signed Written Informed Consent 1.1 Study participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal study participant care.
- 1.2 Study participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
- Target Population 2.1. Untreated patients with multiple myeloma diagnosis to the IMWG diagnostic criteria 2.2. Subject must have documented multiple myeloma as defined by the criteria below:
- Monoclonal plasma cells in the bone marrow ≥10% at some point in their disease history or presence of a biopsy proven plasmacytoma.
- Measurable disease as defined by any of the following:
- IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
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- IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
- Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum Immunoglobulin kappa lambda free light chain ratio.
- ECOG ≤2
- Not eligible for autologous transplantation
- Age 18 years or above
- Reproductive Status
- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for 5 months (30 days plus the time required for durvalumab to undergo five half-lives) after the last dose of study drug.
- Appropriate methods of contraception are:
- female sterilization or tubal ligation (at least 6 weeks prior to the start of the study treatment),
- male sterilization (at least 6 months prior to the start of the study treatment) and/or
- a combination of a hormonal method of contraception with a barrier method or/and
- an intrauterine device or system
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of β-HCG) within one until two weeks prior to the start of durvalumab at time of neoadjuvant treatment and after surgery before starting adjuvant treatment.
- Women will be not be considered to be of childbearing potential if they are post-menopausal and/or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). To be considered post-menopausal the appropriate age-specific requirements have to be met:
- Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution.
- Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago.
- Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving durvalumab and who are sexually active with WOCBP must be willing to adhere to contraception for a period of 7 month post treatment completion.
Who cannot join
- Subject has received any multiple myeloma therapy previously except dexamethasone to a maximum cumulative dose of 160mg, emergency radiotherapy or surgery for symptom control
- Participation in other interventional clinial trials
- Subject has known meningeal involvement of multiple myeloma.
- Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of Screening.
- 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 required for subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of predicted normal.
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- Known moderate or severe persistent asthma, within the past 2 years, 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.
- Use of drugs with significant interaction with or intolerance to the investigational product
- Subject is known to be seropositive for human immunodeficiency virus (HIV)
- active hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or positive HBV DNA)
- Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
- Patients has known current symptomatic congestive heart failure (New York Heart Association Class III-IV), unstable angina pectoris, or cardiac arrhythmia
- Subject has any of the following laboratory test results during the Screening Phase:
- Absolute neutrophil count ≤1.0 × 109/L;
- Platelet count <50 × 109/L
- Aspartate aminotransferase (AST) or alanine aminotransferase level (ALT) ≥2.5 times the upper limit of normal (ULN)
- Alkaline phosphatase level ≥2.5 × ULN
- Total bilirubin level ≥1.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 1.5 × ULN)
- Pregnant women and nursing mothers, or a women who is planning to become pregnant while enrolled in this study or within 3 month after the last dose of daratumumab
- Failure to use highly-effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective:
- Oral hormonal contraception ('pill')
- Dermal hormonal contraception
- Vaginal hormonal contraception (NuvaRing®)
- Contraceptive plaster
- Long-acting injectable contraceptives
- Implants that release progesterone (Implanon®)
- Tubal ligation (female sterilisation)
- Intrauterine devices that release hormones (hormone spiral)
- Double barrier methods This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).
- Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator
- Legally incapictated persons
- Subject is known or suspected of not being able to comply with the study protocol(eg, because of alcoholism, drug dependency, or psychological disorder) or the 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 their well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- Persons held in an institution by legal or official order
Trial locations and contacts
1 site in 1 country.
About this study
Daratumumab for first line treatment of transplant-ineligible myeloma patients followed by daratumumab re-treatment at first relapse (GMMG-DADA)
Read the detailed description
The aim of the study is to investigate the safety and efficacy of daratumumab added to a standard induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCD). A secondary aim is to assess the efficacy of maintenance therapy until progression using daratumumab in combination with bortezomib and dexamethasone. Thirdly the efficacy of a daratumumab-containing regimen at first relapse shall be tested following a daratumumab-containing first line regimen.
Rationale:
VCD has been established as a standard of care for first line therapy of transplant-eligible patients in Germany. The favorable toxicity profile makes this regimen also suitable for transplant-ineligible patients. Daratumumab has shown to be safe and efficacious in a variety of combinations such as with VMP, Vd or Rd. Using a reduced dose of cyclophosphamide the study shall investigate safety and efficacy of Dara-VCD in the transplant-ineligible patient population.
Maintenance therapy has become standard of care in transplant-eligible and non-eligible patients. However, there is uncertainty whether a single agent maintenance is sufficient or whether a combination therapy is necessary. In this study the safety and efficacy of maintenance with daratumumab in combination with bortezomib and dexamethasone will be assessd with a focus on MRD negativity as a novel endpoint.
The multitude of treatment options at first relapse has generated the need to find an optimal sequence of therapy regimens in first and second line. In particular it is unclear whether the efficacy of daratumumab at relapse is affected by its prior use as part of the first line treatment. Patients in this study will relapse on or after a daratumumab-containing maintenance and shall receive DRd at first relapse. In the POLLUX study patients received DRd but had no prior exposure to daratumumab. Therefore, patients included into the POLLUX study can serve as an indirect control cohort for the present study. If in the present study the PFS after DRd is similar to the PFS of the comparable cohort from the POLLUX study, the assumption is supported that prior exposure to daratumumab does not impair the activity of a subsequent daratumumab-containing regimen at relapse. In addition, the overall efficacy of the whole protocol treatment will be assessed by analyzing PFS2 after relapse from study inclusion (PFS2).
- Conditions
- Multiple Myeloma
- Being tested
- Daratumumab
- 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 added to induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCD), to bortezomib and dexamethasone during maintenance and to lenalidomide and dexamethasone at progression/relapse.
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab added to VCd in induction, Vd in maintenance and Rd at relapse | Experimental | Daratumumab at standard dose of 1800 mg will be administered subcutaneously at weekly intervals in cycles 1-2 and every 2 weeks in cycles 3-6 and every 4 weeks in cycles 7-8 together with VCD using bortezomib weekly s.c. for 8 cycles of 28 days each, cyclophosphamide i.v. at 500 mg/m2 on d1 of every cycle and dexamethasone p.o. at 20 mg per week.
Maintenance will be daratumumab subcutaneously every 4 weeks with bortezomib s.c. and dexamethasone 20 mg every 2 weeks until progression or intolerance.
At relapse/progression treatment will be daratumumab 1800 mg subcutaneously weekly during cycle 1-2, every 2 weeks in cycle 3-6 and every 4 weeks thereafter together with lenalidomide 25 mg p.o. day 1-21 and dexamethasone 20-40 mg weekly. Receives: Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of induction therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone (DVCd)
Proportion of patients achieving a very good partial remission (VGPR) or better after 8 cycles of DVCd
Measured: 24 weeks
Secondary outcomes (2)
Assessment of the efficacy of maintenance therapy until progression using daratumumab in combination with bortezomib and dexamethasone.
Proportion of patients with no detectable minimal residual disease as best response to maintenance therapy using daratumumab in combination with bortezomib and dexamethasone
Measured: open
Assessment of the efficacy of a daratumumab-containing regimen at first relapse, following a daratumumab-containing first line regimen.
Progression free survival from first relapse (PFS-R)
Measured: up to 48 months (from first progression/relapse until second progression/relapse or death, whichever occurs first (PFS-R)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2020
- Study start1 Jun 2021
- Primary completion15 Mar 2025
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen-Cilag G.m.b.H
- Responsible party
- Principal investigator, Christoph Scheid, University of Cologne
- Investigators
- Christof Scheid, Prof. Dr., Principal investigator, University of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04656951
- Sponsor's protocol ID
- Uni-Koeln-3946
- Acronym
- GMMG-DADA
- Status last verified
- Mar 2026
- First submitted
- 26 Nov 2020
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Daratumumab for First Line Treatment of Transplant-ineligible Myeloma Patients Followed by Daratumumab Re-treatment at First Relapse
- ClinicalTrials.gov ID
- NCT04656951
- Acronym / sponsor ID
- GMMG-DADA / Uni-Koeln-3946
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Collaborators
- Janssen-Cilag G.m.b.H
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 15 Mar 2025 (actual)
- Study completion
- Dec 2031 (estimated)
- First posted
- 7 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Daratumumab for first line treatment of transplant-ineligible myeloma patients followed by daratumumab re-treatment at first relapse (GMMG-DADA)
Detailed description
The aim of the study is to investigate the safety and efficacy of daratumumab added to a standard induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCD). A secondary aim is to assess the efficacy of maintenance therapy until progression using daratumumab in combination with bortezomib and dexamethasone. Thirdly the efficacy of a daratumumab-containing regimen at first relapse shall be tested following a daratumumab-containing first line regimen.
Rationale:
VCD has been established as a standard of care for first line therapy of transplant-eligible patients in Germany. The favorable toxicity profile makes this regimen also suitable for transplant-ineligible patients. Daratumumab has shown to be safe and efficacious in a variety of combinations such as with VMP, Vd or Rd. Using a reduced dose of cyclophosphamide the study shall investigate safety and efficacy of Dara-VCD in the transplant-ineligible patient population.
Maintenance therapy has become standard of care in transplant-eligible and non-eligible patients. However, there is uncertainty whether a single agent maintenance is sufficient or whether a combination therapy is necessary. In this study the safety and efficacy of maintenance with daratumumab in combination with bortezomib and dexamethasone will be assessd with a focus on MRD negativity as a novel endpoint.
The multitude of treatment options at first relapse has generated the need to find an optimal sequence of therapy regimens in first and second line. In particular it is unclear whether the efficacy of daratumumab at relapse is affected by its prior use as part of the first line treatment. Patients in this study will relapse on or after a daratumumab-containing maintenance and shall receive DRd at first relapse. In the POLLUX study patients received DRd but had no prior exposure to daratumumab. Therefore, patients included into the POLLUX study can serve as an indirect control cohort for the present study. If in the present study the PFS after DRd is similar to the PFS of the comparable cohort from the POLLUX study, the assumption is supported that prior exposure to daratumumab does not impair the activity of a subsequent daratumumab-containing regimen at relapse. In addition, the overall efficacy of the whole protocol treatment will be assessed by analyzing PFS2 after relapse from study inclusion (PFS2).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daratumumab added to VCd in induction, Vd in maintenance and Rd at relapse | Experimental | Drug: DaratumumabDaratumumab at standard dose of 1800 mg will be administered subcutaneously at weekly intervals in cycles 1-2 and every 2 weeks in cycles 3-6 and every 4 weeks in cycles 7-8 together with VCD using bortezomib weekly s.c. for 8 cycles of 28 days each, cyclophosphamide i.v. at 500 mg/m2 on d1 of every cycle and dexamethasone p.o. at 20 mg per week. Maintenance will be daratumumab subcutaneously every 4 weeks with bortezomib s.c. and dexamethasone 20 mg every 2 weeks until progression or intolerance. At relapse/progression treatment will be daratumumab 1800 mg subcutaneously weekly during cycle 1-2, every 2 weeks in cycle 3-6 and every 4 weeks thereafter together with lenalidomide 25 mg p.o. day 1-21 and dexamethasone 20-40 mg weekly. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Signed Written Informed Consent 1.1 Study participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal study participant care.
- 1.2 Study participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
- Target Population 2.1. Untreated patients with multiple myeloma diagnosis to the IMWG diagnostic criteria 2.2. Subject must have documented multiple myeloma as defined by the criteria below:
- ECOG ≤2
- Not eligible for autologous transplantation
Key exclusion criteria (33 listed)
- Subject has received any multiple myeloma therapy previously except dexamethasone to a maximum cumulative dose of 160mg, emergency radiotherapy or surgery for symptom control
- Participation in other interventional clinial trials
- Subject has known meningeal involvement of multiple myeloma.
- Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of Screening.
- 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 subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of predicted normal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaratumumabAlso: DarzalexDaratumumab added to induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCD), to bortezomib and dexamethasone during maintenance and to lenalidomide and dexamethasone at progression/relapse. | Drug | Daratumumab added to VCd in induction, Vd in maintenance and Rd at relapse |
Primary outcome
Efficacy of induction therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone (DVCd)
Time frame: 24 weeks
Proportion of patients achieving a very good partial remission (VGPR) or better after 8 cycles of DVCd
2 secondary outcomes
Assessment of the efficacy of maintenance therapy until progression using daratumumab in combination with bortezomib and dexamethasone.
Time frame: open
Assessment of the efficacy of a daratumumab-containing regimen at first relapse, following a daratumumab-containing first line regimen.
Time frame: up to 48 months (from first progression/relapse until second progression/relapse or death, whichever occurs first (PFS-R)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christof Scheid, Prof. Dr. principal investigator
University of Cologne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab in people with Multiple Myeloma, run by University of Cologne at 1 site in Germany.
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 23 inclusion and 33 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: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. 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 Germany. 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?
This study is still under way. Results are not available in the source record yet.
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?
Efficacy of induction therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone (DVCd) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2026.