Efficacy of daratumumab (Dara) retreatment of relapsed/ refractory multiple myeloma (RRMM) patients in combination with panobinostat, bortezomib-and dexamethasone
- Conditions
- Relapsed and refractory multiple myelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000382-16-DE
- Lead Sponsor
- Medical Center - University of Freiburg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
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 <3.5 mmol/L (<14 mg/dL)
6.Women of childbearing potential (WOCBP) must have 2 negative serum pregnancy tests, one 10-14 days prior to start of the study drugs and one within 24 hours prior to the start of study drugs. Women must not be breastfeeding. WOCBP must agree to follow instructions for methods of contraception for 4 weeks before the start of treatment with study drugs, for the duration of treatment with study drugs, and for a total of 3 months after cessation of daratumumab treatment. Males who are sexually active with WOCBP must always use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy.
7.Written informed consent obtained according to international guidelines and local laws;
8.Ability to understand the nature of the trial and comply with the trial related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.<br>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:<br>• Characterize the response to Dara-PanVD, response duration, PFS, OS<br>and QoL and fitness (according to R-MCI) in RR MM pts<br>• Assess the phenotype, CD38-expression, MRD, mass cytometry and<br>sequencing analyses (biomarker correlation analysis) in RRMM treated<br>with Dara-PanVD.<br>• Comparison of tolerance, efficacy and CD38 preservation of Dara-PanV<br>vs. Dara-V maintenance from cycle 9 onwards until PD.;Primary end point(s): Response to Dara-PanVD, <br>;Timepoint(s) of evaluation of this end point: within 2 weeks after end of cycle 8
- Secondary Outcome Measures
Name Time Method