Daratumumab for first line treatment of transplant-ineligible myeloma patients followed by daratumumab re-treatment at first relapse (GMMG-DADA)
- Conditions
- Multiple Myeloma
- Registration Number
- 2024-517761-17-00
- Lead Sponsor
- University Of Cologne
- Brief Summary
The aim of the trial is to investigate the safety and efficacy of daratumumab added to a standard induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCd).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 67
Signed Written Informed Consent
Male trial participants who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year and must be willing to adhere to any approved contraception method for a period of 6 months post treatment completion.
Untreated patients with multiple myeloma diagnosis according to the International myeloma working group (IMWG) diagnostic criteria
ECOG ≤2
Not eligible or willing for autologous transplantation
Age 18 years or above
Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for 6 months after the last dose of IMP.
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of β-HCG) within one to two weeks prior to the start of Daratumumab
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 must not be breastfeeding.
Subject has received any multiple myeloma therapy previously, except dexamethasone to a maximum cumulative dose of 160mg, emergency radiotherapy or surgery for symptom control
Subject has any concurrent medical condition or disease (e.g. active systemic infection) that is likely to interfere with trial procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this trial.
Concomitant chemotherapy or myeloma-specific therapy other than trial treatment (incl. standard intensification) is not permitted. The sponsor must be notified in advance (or as soon as possible thereafter) of any instances on which prohibited medications are administered.
Patients has known current symptomatic congestive heart failure (New York Heart Association Class III-IV, see APPENDIX III B) unstable angina pectoris, or uncontrolled cardiac arrythmia
Absolute neutrophil count ≤0.5 × 109/L
Platelet count <30 × 109/L
Aspartate aminotransferase (AST) or alanine aminotransferase level (ALT) ≥4.5 times the upper limit of normal (ULN)
Alkaline phosphatase level ≥4.5 × ULN
Total bilirubin level ≥2.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 1.5 × ULN)
Pregnant women and nursing mothers, or women planning to become pregnant while enrolled in this trial or within 3 months after the last dose of daratumumab
Failure to use highly-effective contraceptive methods.
Participation in other interventional clinical trials
Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator
Legally incapacitated persons
Subject is known or suspected of not being able to comply with the trial protocol (e.g. 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 (e.g. 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
Subject has known meningeal involvement of multiple myeloma.
Subjects with plasma cell leukemia or AL amyloidosis
Non-hematologic malignancy within the past 2 years with the exception defined in the protocol
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.
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 trial.
Subject is known to be seropositive for human immunodeficiency virus (HIV)
Active hepatitis B (defined by a positive test for HBV DNA) or hepatitis C (defined by a positive test for HCV-RNA-quantification). (Patients with a positive test for HBs antigen or antibodies, but negative HBC DNA may be included but must be monitored for HBV activation throughout the study.)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Response (≥VGPR) after 8 cycles of DVCd Response (≥VGPR) after 8 cycles of DVCd
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Overall survival (OS)
Progression-free survival from trial inclusion (PFS) Progression-free survival from trial inclusion (PFS)
Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at a level of 10e-5 Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at a level of 10e-5
Progression-free survival at 12 months from start of second line therapy Progression-free survival at 12 months from start of second line therapy
Time to next treatment (TTNT) Time to next treatment (TTNT)
Overall response rate of first line treatment Overall response rate of first line treatment
Overall response rate of second line treatment Overall response rate of second line treatment
Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at other thresholds or by Flow Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at other thresholds or by Flow
Trial Locations
- Locations (15)
Kommunale Traegergesellschaft Cottbus mbH
🇩🇪Cottbus, Germany
Rems-Murr-Kliniken gGmbH
🇩🇪Winnenden, Germany
Johanniter GmbH
🇩🇪Bonn, Germany
Centrum für Hämatologie und Onkologie Bethanien
🇩🇪Frankfurt am Main, Germany
University Hospital Cologne AöR
🇩🇪Cologne, Germany
Universitaetsklinikum Tuebingen AöR
🇩🇪Tuebingen, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Klinikum Esslingen GmbH
🇩🇪Esslingen Am Neckar, Germany
Klinikum der Universitaet Muenchen AöR
🇩🇪Munich, Germany
OnkoMed GbR Dr. M. Neise, Dr. A. Lollert, Dr. D. Neise
🇩🇪Krefeld, Germany
Scroll for more (5 remaining)Kommunale Traegergesellschaft Cottbus mbH🇩🇪Cottbus, GermanyMartin Schmidt-HieberSite contact0355462220m.schmidt-hieber@mul-ct.de