Carfilzomib for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy per IMWG criteria: • Patients must have received no prior chemotherapy for this disease; • patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis); • prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration and ≤ 160 mg dexamethasone; • patients must not have received any prior treatment with bortezomib or lenalidomide\n- ANC ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥ 75 x 109/L.\n- Calculated creatinine clearance (by Cockroft-Gault) ≥ 50 mL/min or serum creatinine below 2 g/dL\n- Female of child bearing potential (FCBP) must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide. The first pregnancy test must be performed within 10-14 days before and the second pregnancy test must be performed within 24 hours before lenalidomide is prescribed for Cycle 1 (prescriptions must be filled within 7 days).\n- FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 30 days after discontinuation from the study.\n- Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 90 days following discontinuation from the study even if he has undergone a successful vasectomy.\n- All study participants in the US and EU countries (excluding Poland) must be consented to and registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®.\n- Subjects must comply with pregnancy prevention and counseling\n- Voluntary written informed consent.\n- Both transplant and non-transplant candidates are eligible. Transplant candidates must agree at time of consent to defer transplant to the end of study treatment. If patient proceeds to transplant, they will come off study.\n- Diagnosis of symptomatic multiple myeloma as per current IMWG uniform criteria prior to initial treatment\n- Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma\n- Measurable disease, prior to initial treatment as indicated by one or more of the following: • Serum M-protein ≥ 1 g/dL • Urine M-protein ≥ 200 mg/24 hours • Involved serum free light chains ≥ 10 mg/dL provided that free light chain ratio is abnormal • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable\n- Bone marrow specimen will be required at study entry; available DNA sample from pre-treatment BM will be used for calibration step for MRD evaluation by gene sequencing.\n- Males and females ≥ 18 years of age\n- ECOG performance status of 0-2\n- Adequate hepatic function, with bilirubin ≤ 1.5 x ULN and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 xULN"}

Exclusion criteria

• {"criterion_text":"- Frail, non-transplant candidates, per modified IMWG frailty score (age not counted as a scoring factor)\n- Peripheral neuropathy ≥ Grade 2 at screening\n- Diarrhea > Grade 1 in the absence of antidiarrheals\n- CNS involvement\n- Patients who cannot undergo or unwilling to take thromboprophylaxis\n- Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF< 40%, within 6 months prior to first dose.\n- Pregnant or lactating females\n- Major surgery within 3 weeks prior to first dose.\n- Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities\n- Pulmonary embolism within 6 months prior to first dose.\n- Known moderate or severe persistent asthma or known chronic obstructive pulmonary disease (COPD)\n- Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as <1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein and and FLC <10mg/dL as per IMWG measured by Freelite.\n- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening\n- Uncontrolled diabetes\n- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose\n- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or are asymptomatic chronic carriers of HBV are eligible.\n- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone\n- Any clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent.\n- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)\n- Amyloidosis\n- Plasma cell leukemia\n- Waldenström’s macroglobulinemia or IgM myeloma\n- Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)\n- Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater\n- Patients not able to tolerate bortezomib, carfilzomib, lenalidomide or dexamethasone"}

Primary endpoints

• {"endpoint_text":"- The MRD-negative complete response status at 12 months by NGS and PFS defined as the time to progressive disease or death as defined by IMWG criteria","definition_or_measurement_approach":"MRD-negative complete response status assessed at 12 months by NGS; PFS defined as time to progressive disease or death as defined by IMWG criteria."}

Secondary endpoints

• {"endpoint_text":"- The MRD-negative status in each study arm at 8and 24 months","definition_or_measurement_approach":"MRD-negative status assessed at 8 and 24 months (by NGS as per primary endpoint methodology)."}
• {"endpoint_text":"- Duration of MRD-negative status.","definition_or_measurement_approach":"Time from achieving MRD-negative status until recurrence of detectable disease per MRD assessment."}
• {"endpoint_text":"- MRD-negative complete response","definition_or_measurement_approach":"Assessment of complete response with MRD negativity (methodology as per IMWG and NGS MRD assessment)."}
• {"endpoint_text":"- Comparing rate of PR or better, VGPR or better, CR or better, or sCR at 8, 12, 24, 36, 48, and 60 months and as best response between the two arms","definition_or_measurement_approach":"Response rates (PR, VGPR, CR, sCR) determined at specified landmark timepoints using IMWG response criteria."}
• {"endpoint_text":"- Determine rates of improvement of the depth of response by at least one category according to IMWG response criteria. (For example, an improvement from very good partial response (VGPR) to near complete response (nCR) or better than nCR including conversion from CR to MRD negative disease [overall response]) at specified landmark timepoints.","definition_or_measurement_approach":"Improvement in depth of response assessed using IMWG response categories at specified landmark timepoints."}
• {"endpoint_text":"- To compare overall survival.","definition_or_measurement_approach":"Overall survival measured as time from randomization to death from any cause."}
• {"endpoint_text":"- Safety and tolerability of KRd vs. VRd","definition_or_measurement_approach":"Safety and tolerability assessed by frequency and severity of adverse events and other safety measures across treatment arms."}

Norway

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

11-12-2024

Processing Time Days

41

Number Of Sites

2

Number Of Participants

20

Finland

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

12-12-2024

Processing Time Days

42

Number Of Sites

1

Number Of Participants

10

Poland

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

16-12-2024

Processing Time Days

46

Number Of Sites

8

Number Of Participants

203

Primary sponsor

Full Name

Polish Myeloma Consortium

Organisation Type

Patient organisation/association

Country Of Registered Address

Poland

Third parties

• {"country":"Poland","full_name":"Kapadi Sp. z o.o.","duties_or_roles":"codes: 1,12","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Optimapharm Nordic Oy","duties_or_roles":"codes: 1,12","organisation_type":"Pharmaceutical company"}