Multiple Myeloma patients with relapsed or relapsed/refractory disease with the presence of del(17p) in the plasma cell clone MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Daratumumab
Product Code: [NA]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
Current Sponsor code: Daratumumab
Concentration unit: mg millig
Sponsors
Fondazione EMN Italy Onlus
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient has given voluntary written informed consent. - Subject must be at least 18 years of age. - Subject must have documented MM. - Subject must have del(17p) observed by FISH in at least 10% of bone marrow plasma cells at any time of MM history. - Subject must have serum monoclonal paraprotein (M-protein) level >=0.5 g/dL or urine M-protein, level >= 200 mg/24 hours, or light chain MM, or serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio. - Subject must have received at least 1 and no more than 3 prior lines of therapy for MM. - Subject must have received at least 2 consecutive cycles of lenalidomide in a previous line of therapy. - Subject must have achieved a response (PR or better) to at least one prior regimen. - Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy. - Subject must have an ECOG Performance Status score of 0, 1, or 2. - Subject must have the following laboratory values: ¿ Platelet count >=50 x 109/L (>=30 x 109 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration). ¿ Absolute neutrophil count (ANC) >= 1 x 109/L without the use of growth factors. ¿ Corrected serum calcium = 15 mL/minute - Females of childbearing potential (FBCP) must follow the Pregnancy Prevention Plan and use a highly effective and an additional barrier contraception method simultaneously for 28 days before starting pomalidomide, during treatment and dose interruptions, for at least 28 days after the last dose of pomalidomide and 3 months after the last dose of daratumumab - Males must use an effective barrier method of contraception if sexually active with FCBP for at least 28 days before starting pomalidomide, during the treatment and dose interruptions, for at least 28 days after the last dose of pomalidomide and 3 months after the last dose of daratumumab. Male subjects must agree to refrain from sperm donation for at least 3 months after the last dose of daratumumab. 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Subject has received daratumumab or other anti-CD38 monoclonal antibody previously. - Subject’s disease shows evidence of refractoriness or intolerance to pomalidomide. If previously treated with a pomalidomide-containing regimen, the subject is excluded if he or she: ¿ Discontinued due to any adverse event related to prior pomalidomide treatment, or ¿ If, at any time point, the subject was refractory to any dose of pomalidomide. Refractory to pomalidomide is defined either: ¿ Subjects whose disease progresses within 60 days of pomalidomide; or ¿ Subjects whose disease is nonresponsive while on lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an MR or development of PD while on pomalidomide. - Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of enrollment. - Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 16 weeks prior to initiation of study treatment and are currently dependent on such treatment. - Subjects unable or unwilling to undergo antithrombotic prophylactic treatment. - Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, in agreement with the medical monitor, is considered cured with minimal risk of recurrence within 3 years). - Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second (FEV1) 500 msec.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of DPd efficacy.;Secondary Objective: Evaluation of DPd additional efficacy parameters, and response related features in terms of responses and survival (please refer to secondary endpoints). Explorative Objectives Biological studies aiming at describing the biological characteristics of MM with del(17p), the disease evolution, and clonal dynamics during therapy and at relapse.;Primary end point(s): The primary endpoint of the study is efficacy in terms of: -Achievement of molecular minimal residual disease (MRD) 10-5 negativity rate assessed by means of next-generation sequencing (ClonoSEQ assay) in patients attaining a complete remission in the first year of treatment.;Timepoint(s) of evaluation of this end point: 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS will be measured from the start of treatment to the date of first observation of disease progression or death to any cause as an event. Subjects who withdraw from the study will be considered censored at the time of the last complete disease assessment. Subjects who complete the study, have no progressed, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to follow-up prior to the end of the study have no progressed, and are still alive will also be censored at the time of last contact.; Overall response rate (ORR) ORR will include at least PR using the International Response Criteria reported by Durie et al. Categories of response will include stringent Complete Response (sCR), CR, VGPR, PR, SD and PD. If, during the course of the study, other relevant categories are identified in the literature, then these categories may be added. Responders are defined as subjects with at least a PR.; Progression free survival 2 (PFS2): PFS2 will be measured from the start of treatment to the date of observation of second disease progression (i.e. progression after the second line of therapy) or death to any cause as an event. In case of date of second progression is not available, date of start of third line treatment can be used. Subjects who withdraw from the study will be considered at the time of the last complete disease assessment. Subjects who complete the study, have no progressed, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to follow-up prior to the end of the study have no progressed, and are still alive will also be censored at the time of last contact; Duration of response (DoR) Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to follow-up, at the time of death due to other cause than PD, or at the end o | — |
Countries
Italy
Contacts
Public ContactClinical Trial Office
Fondazione EMN Italy Onlus
Outcome results
None listed