Relapsed and refractory multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Daratumumab (DARZALEX® 1.800 mg Injektionslösung)
Product Name: Darzalex
Product Code: L01XC24
Pharmaceutical Form: Concentrate for solution for injection
Trade Name: Farydak (Panobinost
Sponsors
Medical Center - University of Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients =18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 3. Patients with a confirmed diagnosis of multiple myeloma (in line with the revised IMWG criteria) who have received Dara-Rd as relapse treatment in 2nd line and have documented evidence of PD based on the investigator’s determination of response as defined by the IMWG uniform response criteria. (Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study) 4. Must have measurable disease defined by at least 1 of the following 3 measurements: ? Serum M-protein =0.5 g/dL ? Urine M-protein =200 mg/24 hours OR ? Serum Free Light Chain (FLC) >100 mg/L of involved FLC 5. Laboratory test results within these ranges: • White blood cell count =2 x 109/L • Absolute neutrophil (ANC) count =0.5 x 109/L • Platelet count =75 x 109/L • Haemoglobin >8 g/dL • Calculated creatinine clearance (according to MDRD) =30 mL/minute • Total bilirubin =1.5 x upper limit of normal (ULN) • AST and ALT =2.5 x ULN • Corrected serum calcium level =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Plasma cell leukaemia, and/or extensive EM relapse (=multiple, large sites); entirely refractory MM disease, documented systemic light chain amyloidosis, MM involving the central nervous system 2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Waldenström’s macroglobulinemia or IgM myeloma 4. Clinical signs of meningeal involvement of multiple myeloma 5. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted. (FEV1 testing is, required during screening) 6. Known intolerance to or contraindication for the use of bortezomib, or refractory to bortezomib (defined as progressive disease according to IMWG criteria 7. Known intolerance to or contraindication for the use of daratumumab, panobinostat, and dexamethasone or any of the other ingredients in the study treatment formulations (known hypersensitivity to the active substances or any of the excipients) 8. Life expectancy of <4 months 9. Major surgery within 4 weeks prior to cycle 1 day 1 10. Subject is known to be seropositive for human immunodeficiency virus (HIV) or has active hepatitis (type A, B or hepatitis C) 11. Any serious underlying medical condition, such as: • serious active viral, bacterial, or uncontrolled systemic fungal infection • severe cognitive disorders • severe ventricular arrhythmia 12. Participation in any other interventional clinical trial within the last 30 days before the start of this trial 13. Any prior or concurrent malignancy other than multiple myeloma. Exceptions include patients who have been disease-free for at least five years before study entry or patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer 14. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial 15. Known or persistent abuse of medication, drugs or alcohol; Subject is known or suspected of not being able to comply with study protocol 16. Current or planned pregnancy, nursing period 17. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception Women of childbearing potential can only take part in this study if the risk of becoming pregnant is absolutely minimized. Save contraceptive methods comprise: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception and have to be used while participating in the study. Men must agree to use a latex condom during sexual contact with females of childbearing potential while participating in this study even if he has undergone a successful vasectomy. Patients must abstain from donating blood, semen, or sperm during participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is a first evaluation of Dara-retreatment, applying a sensibly-dosed and well-tolerable 4-agent combination schedule of Dara s.c., with regard to efficacy and treatment longevity. Dara-panobinostat (Pan) bortezomib (V) dexamethasone (D) should therefore be equally potent to Dara-VD in pts with 2 prior lines in the CASTOR-trial;Secondary Objective: Secondary study objectives will be analysed descriptively: • Characterize the response to Dara-PanVD, response duration, PFS, OS and QoL and fitness (according to R-MCI) in RR MM pts • Assess the phenotype, CD38-expression, MRD, mass cytometry and sequencing analyses (biomarker correlation analysis) in RRMM treated with Dara-PanVD. • Comparison of tolerance, efficacy and CD38 preservation of Dara-PanV vs. Dara-V maintenance from cycle 9 onwards until PD.;Primary end point(s): Response to Dara-PanVD, ;Timepoint(s) of evaluation of this end point: within 2 weeks after end of cycle 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS), Progression-free survival (PFS), response duration, Minimal residual disease (MRD), Quality of Life (QoL), fitness assessment via R-MCI, safety (grade 3/4 toxicities under Dara-PanVD according to National cancer institute – common terminology criteria for adverse events (NCI-CTCAE) version 5.0, adverse events, serious adverse events. Early death within initial 6 + 12 months, biomarker studies before, during and at end of the study medication. Treatment longevity assessed as number of Dara-PanVD / Dara-(Pan)V cycles given.;Timepoint(s) of evaluation of this end point: OS and PFS calculated as time from start of treatment until death or first observation of PD. Patients without an event of interest will be considered as censored observations at the time last seen alive/without observation of disease progression. OS and PFS will be estimated using the Kaplan Meier method. The comparison of QoL pre- and posttreatment will be evaluated with the Wilcoxon’s signed rank test in patients where both assessments are available. The analysis of the randomized part of this trial will be considered as exploratory. OS, PFS (calculated from randomization) will be compared between randomized groups based on the Intention-to-treat-principle, i.e. all randomized patients will be analysed irrespective of protocol deviations in the treatment group they were allocated to. | — |
Countries
Germany
Contacts
Public ContactDepartment for Medicine I, ECTU
Medical Center - University of Freiburg
Outcome results
None listed