DARATUMUMAB for Primary plasma cell leukemia

Inclusion criteria

• {"criterion_text":"- Female or male patients of any race or ethnicity, aged between 18 and 80 years (inclusive) at the time of signing the ICF."}
• {"criterion_text":"- If females of childbearing potential (FCBP)*, the following apply: 10.1 Willingness to use an acceptable form of birth control 10.2 They must agree not to donate eggs 10.3 They must have 2 negative serum or urine pregnancy tests"}
• {"criterion_text":"- If male subjects of reproductive potential who are sexually active with FCBPs the following apply. 11.1 Must always use a latex or synthetic condom during the study and for 3 months (90 days) after discontinuing study treatment (even if they have undergone a successful vasectomy). 11.2 They must not donate sperm during the study or for 3 months after the last dose of study treatment."}
• {"criterion_text":"- Patients who are able to comprehend and willing to follow the requirements of the study (including adherence to the study-specific prohibitions and restrictions and availability on scheduled visit dates)."}
• {"criterion_text":"- Patients (or patients' legally acceptable representative as applicable) who are able to understand and willing to provide voluntary written informed consent before any clinical trial-related procedure is performed."}
• {"criterion_text":"- Patients newly diagnosed with documented pPCL as defined by the current IMWG criteria for PCL and MM [5,34]: 2.1 Documented presence of ≥5% PBPCs and/or absolute number ≥ 0.5 × 103/μL (by flow cytometry) 2.2 Clonal BMPCs ≥10% or biopsy-proven bony or extramedullary plasmacytoma (EMP) 2.3 At least one of the following myeloma defining events (CRAB or malignancy biomarkers criteria - Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following): a) Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL) b) Renal insufficiency: Creatinine clearance (CrCl) <40 mL/min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL) c) Anemia: hemoglobin value of >20 g/L below the lower limit of normal (LLN), or a hemoglobin value <100 g/L d) Bone lesions: One or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT. - Any one or more of the following biomarkers of malignancy: a) Clonal bone marrow plasma cell percentage ≥60% b) Involved:Uninvolved serum free light chain (sFLC) ratio ≥100 c) >1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)."}
• {"criterion_text":"- Measurable disease by protein electrophoresis as defined by any of the following: 3.1 Serum M-protein level: - For IgG MM: ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours - For IgA, IgE and IgM MM: ≥0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours - For IgD MM: ≥0.05 g/dL or urine M-protein level ≥200 mg/24 hours 3.2 Light chain MM without measurable disease in the serum or the urine: sFLC ≥10 mg/dL (involved light chain) and abnormal sFLC κ/λ ratio."}
• {"criterion_text":"- Patients for whom high-dose therapy, with or without stem cell transplantation, is part of the intended treatment plan."}
• {"criterion_text":"- Patient not currently or previously treated with any systemic therapy or stem cell transplant for any plasma cell dyscrasia, apart from a short course of corticosteroid therapy (equivalent of dexamethasone 40 mg/day for up to 4 days)."}
• {"criterion_text":"- Adequate bone marrow function as determined by the following: 6.1 Hemoglobin ≥7.0 g/dL [≥4.34 mmol/L; prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted] 6.2 Absolute neutrophil count (ANC) ≥1.0 x 109/L 6.3 Platelet count ≥50 x 109/L if disease involvement in bone marrow is >50%; otherwise ≥75% x 109/L."}
• {"criterion_text":"- Adequate liver function as determined by the following: 7.1 Serum Aspartate Transaminase (AST) ≤2.5 x ULN 7.2 Serum Alanine Aminotransferase (ALT) ≤2.5 x ULN 7.3 Total bilirubin ≤1.5 x ULN"}
• {"criterion_text":"- Adequate renal function as determined by estimated CrCl ≥20 mL/min"}
• {"criterion_text":"- Performance status (PS) according to (ECOG) 0-3"}

Exclusion criteria

• {"criterion_text":"- Patients with secondary PCL."}
• {"criterion_text":"- Any of the following: 10.1 Known seropositivity for human immunodeficiency virus (HIV) 10.2 Seropositivity for hepatitis B virus (HBV) 10.3 Known seropositivity for hepatitis C virus (HCV)"}
• {"criterion_text":"- Clinically significant cardiac disease including: 11.1 Myocardial infarction within 6 months before study treatment initiation (C1D1) 11.2 Unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association [NYHA] Class III-IV) 11.3 Pericardial disease 11.4 Cardiac amyloidosis 11.5 Uncontrolled cardiac arrhythmia (NCI CTCAE v5 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities 11.6 Screening 12-lead ECG showing a baseline QT interval >470 msec (except for subjects with pacemaker) 11.7 Screening transthoracic echocardiogram (TTE) showing left ventricular ejection fraction (LVEF) <40% (screening TTE is required only for subjects aged ≥ 65 years)"}
• {"criterion_text":"- Receipt of a strong CYP3A4 inducer (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital and St. John's Wort) within 5 half-lives prior to study treatment initiation"}
• {"criterion_text":"- Known allergies, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective SmPCs and Investigator's Brochure [IB]), or known sensitivity to mammalian-derived products"}
• {"criterion_text":"- Gastrointestinal disease that may significantly affect the absorption of oral drugs as per Investigator's discretion"}
• {"criterion_text":"- Vaccination with live attenuated vaccines within 4 weeks of study treatment initiation"}
• {"criterion_text":"- Major surgery within 2 weeks before study treatment initiation or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to start the study treatment"}
• {"criterion_text":"- Concurrent use of other anti-cancer agents/treatments"}
• {"criterion_text":"- Subject is known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder). 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 the well-being) or that could prevent, limit, or confound the protocol-specified assessments"}
• {"criterion_text":"- Females who are pregnant, breast feeding, or planning to become pregnant while enrolled in this study or within 3 months following the last dose of any component of the study treatment"}
• {"criterion_text":"- Prior or concurrent invasive malignancy (other than PCL) within 5 years of date of study treatment initiation except for the following: 2.1 Malignancy treated with curative intent and with no known active disease present for ≥3 years before study treatment initiation. 2.2 Adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix or breast, incidental histologic finding of prostate cancer (T1a or T1b) or other non-invasive lesion that, as per Investigator's judgement, is considered cured with minimal risk of recurrence over the next 3 years."}
• {"criterion_text":"- Males who plan to father a child while enrolled in this study or within 3 months following the last dose of any component of the study treatment."}
• {"criterion_text":"- Patients who currently receive treatment with any investigational drug/vaccine/device/intervention or who have received any investigational product within 30 days or 5 half-lives of the investigational agent (whichever is longer) before the screening"}
• {"criterion_text":"- Contraindications to the use of any components of the study treatment (daratumumab, bortezomib, dexamethasone, cyclophosphamide, doxorubicin) per local prescribing information (SmPCs)"}
• {"criterion_text":"- Radiation therapy within 14 days before study treatment initiation."}
• {"criterion_text":"- Plasmapheresis within 28 days before study treatment initiation."}
• {"criterion_text":"- Exhibiting clinical signs of meningeal or central nervous system involvement by PCL."}
• {"criterion_text":"- Patients with peripheral neuropathy or neuropathic pain Grade 2 or higher"}
• {"criterion_text":"- Concurrent systemic amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes), active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease, and any other medical condition/disease that is likely to interfere with the study procedures or results, or that in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study"}
• {"criterion_text":"- Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second [FEV1] <50% of predicted normal"}
• {"criterion_text":"- Known moderate or severe persistent asthma within the past 2 years (refer to Appendix 2), or the patient currently has uncontrolled asthma of any classification"}

Primary endpoints

• {"endpoint_text":"- PFS: Duration from the date of induction treatment initiation to the date of first documented evidence of progressive disease (PD) (assessed by the IMWG criteria or death, whichever occurs earlier.","definition_or_measurement_approach":"Duration from the date of induction treatment initiation to the date of first documented evidence of progressive disease (PD) assessed by the IMWG criteria or death, whichever occurs earlier."}

Secondary endpoints

• {"endpoint_text":"- Proportions of patients achieving PR or better, VGPR or better, and sCR or CR (as determined by the IMWG criteria)","definition_or_measurement_approach":"Response categories (PR, VGPR, sCR, CR) determined by IMWG criteria."}

Greece

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

09-12-2024

Processing Time Days

80

Number Of Sites

7

Number Of Participants

43

Primary sponsor

Full Name

Hellenic Society Of Hematology

Organisation Type

Patient organisation/association

Country Of Registered Address

Greece

Third parties

• {"country":"Greece","full_name":"Optimapharm Greece Consulting Research Single Member S.A.","duties_or_roles":"codes:1,10,11,12,2,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.; ECG analysis/ review; Routine clinical pathology testing; code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"National And Kapodistrian University Of Athens","duties_or_roles":"Μultiparametric Flow Cytometry","organisation_type":"Educational Institution"}