Daratumumab for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Signed Written Informed Consent\n- 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.\n- Untreated patients with multiple myeloma diagnosis according to the International myeloma working group (IMWG) diagnostic criteria\n- ECOG ≤2\n- Not eligible or willing for autologous transplantation\n- Age 18 years or above\n- 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.\n- 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\n- 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.\n- Women must not be breastfeeding."}

Exclusion criteria

• {"criterion_text":"- Subject has received any multiple myeloma therapy previously, except dexamethasone to a maximum cumulative dose of 160mg, emergency radiotherapy or surgery for symptom control\n- 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.\n- 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.\n- 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\n- Absolute neutrophil count ≤0.5 × 109/L\n- Platelet count <30 × 109/L\n- Aspartate aminotransferase (AST) or alanine aminotransferase level (ALT) ≥4.5 times the upper limit of normal (ULN)\n- Alkaline phosphatase level ≥4.5 × ULN\n- Total bilirubin level ≥2.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 1.5 × ULN)\n- 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\n- Failure to use highly-effective contraceptive methods.\n- Participation in other interventional clinical trials\n- Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator\n- Legally incapacitated persons\n- 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.\n- Persons held in an institution by legal or official order\n- Subject has known meningeal involvement of multiple myeloma.\n- Subjects with plasma cell leukemia or AL amyloidosis\n- Non-hematologic malignancy within the past 2 years with the exception defined in the protocol\n- 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.\n- 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.\n- Subject is known to be seropositive for human immunodeficiency virus (HIV)\n- 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.)"}

Primary endpoints

• {"endpoint_text":"- Response (≥VGPR) after 8 cycles of DVCd","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at a level of 10e-5","definition_or_measurement_approach":"Assessed by NGS at a level of 10e-5"}
• {"endpoint_text":"- Progression-free survival at 12 months from start of second line therapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival from trial inclusion (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to next treatment (TTNT)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall response rate of first line treatment","definition_or_measurement_approach":"Overall response rate assessed using the IMWG response criteria (per trial secondary objectives)"}
• {"endpoint_text":"- Overall response rate of second line treatment","definition_or_measurement_approach":"Overall response rate assessed using the IMWG response criteria (per trial secondary objectives)"}
• {"endpoint_text":"- Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at other thresholds or by Flow","definition_or_measurement_approach":"Assessed by NGS at other thresholds or by Flow cytometry"}

Germany

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

548

Number Of Sites

15

Number Of Participants

67

Primary sponsor

Full Name

University Of Cologne

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"University Of Cologne","duties_or_roles":"1,6,7,8","organisation_type":"Educational Institution"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}