Daratumumab for Multiple myeloma (relapsed and/or refractory)|Multiple myeloma with del(17p)

Inclusion criteria

• {"criterion_text":"- Patient has given voluntary written informed consent."}
• {"criterion_text":"- Subject must have an ECOG Performance Status score of 0, 1, or 2."}
• {"criterion_text":"- Subject must have the following laboratory values: a)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); b) Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors; c) Corrected serum calcium ≤14 mg/dL (3.5 mmol/L); d) Alanine transaminase (ALT): ≤ 3 x the upper limit normal (ULN); e) Total bilirubin: ≤ 2 x the ULN; f) Calculated or measured creatinine clearance: ≥ 15 mL/minute."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subject must be at least 18 years of age."}
• {"criterion_text":"- Subject must have documented MM."}
• {"criterion_text":"- Subject must have del(17p) observed by FISH in at least 10% of bone marrow plasma cells at any time of MM history."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subject must have received at least 1 and no more than 3 prior lines of therapy for MM."}
• {"criterion_text":"- Subject must have received at least 2 consecutive cycles of lenalidomide in a previous line of therapy."}
• {"criterion_text":"- Subject must have achieved a response (PR or better) to at least one prior regimen."}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- Subject has received daratumumab or other anti-CD38 monoclonal antibody previously."}
• {"criterion_text":"- Subject has clinically significant cardiac disease, including: a) Myocardial infarction within 6 months before Cycle 1, Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class IIIIV); b) Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Version 4 Grade 2 or higher) or clinically significant ECG abnormalities. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >500 msec."}
• {"criterion_text":"- 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: a) 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. b) 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."}
• {"criterion_text":"- Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic halflives of the treatment, whichever is longer, before the date of enrollment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subjects unable or unwilling to undergo antithrombotic prophylactic treatment."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second (FEV1) <60% of predicted normal), asthma, or a history of asthma within the last 2 years. Subjects with known or suspected COPD must have a forced expiratory volume (FEV) test during Screening."}
• {"criterion_text":"- Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV antibody positive or HCV-RNA quantitation positive)."}
• {"criterion_text":"- Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study."}

Primary endpoints

• {"endpoint_text":"- 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 nextgeneration sequencing (ClonoSEQ assay) in patients attaining a complete remission in the first year of treatment.","definition_or_measurement_approach":"MRD 10^-5 negativity rate assessed by next-generation sequencing (ClonoSEQ assay) in patients attaining a complete remission within the first year of treatment."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured from start of treatment to date of first documented disease progression or death from any cause."}
• {"endpoint_text":"- Overall response rate (ORR).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression free survival 2 (PFS2).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response (DoR).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to the next anti-myeloma therapy (TNT).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Subgroup analyses: MRD negativity rate and prognostic factors.","definition_or_measurement_approach":""}

Italy

Earliest CTIS Part Ii Submission Date

27-06-2023

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

1017

Number Of Sites

13

Number Of Participants

45

Primary sponsor

Full Name

Fondazione European Myeloma Network Italy O.N.L.U.S.

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Mipharm S.p.A.","duties_or_roles":"Drug dispenser","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Emn Trial Office S.r.l. Impresa Sociale","duties_or_roles":"Shipping samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Celgene International II S.a.r.l.","duties_or_roles":"Drug supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Janssen Pharmaceutica","duties_or_roles":"Drug supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Humanitas Research Hospital","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Drug dispenser","organisation_type":"Pharmaceutical company"}