Carfilzomib for Smoldering multiple myeloma | Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria: Serum M-protein ≥3 g/dl or urinary monoclonal protein >500 mg per 24 hours and/or Absence of CRAB symptoms and myeloma defining events"}
• {"criterion_text":"- Written informed consent"}
• {"criterion_text":"- Calculated Creatinine Clearance ≥ 50 ml/min"}
• {"criterion_text":"- Patient is capable of giving informed consent"}
• {"criterion_text":"- Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic and/or the PETHEMA criteria"}
• {"criterion_text":"- Measurable disease"}
• {"criterion_text":"- Age >18 years"}
• {"criterion_text":"- WHO/ECOG performance status <=2"}
• {"criterion_text":"- Patients must have normal organ and marrow function"}
• {"criterion_text":"- Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all premenopausal women) Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Plan"}
• {"criterion_text":"- Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to entry and again within 24 hours of starting lenalidomide treatment"}

Exclusion criteria

• {"criterion_text":"- Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)"}
• {"criterion_text":"- Significiant cardiovascular disease with NYHA grade III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia"}
• {"criterion_text":"- Active hepatitis B or C infection"}
• {"criterion_text":"- Known or suspected HIV infection"}
• {"criterion_text":"- Incidence of gastrointestinal disease that would prevent absorption"}
• {"criterion_text":"- Patients with gastric or duodenal ulcers"}
• {"criterion_text":"- Significant neuropathy ≥Grade 3 or grade 2 with pain within 14 days of enrollment"}
• {"criterion_text":"- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection."}
• {"criterion_text":"- History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years"}
• {"criterion_text":"- Major surgery within 1 month prior to enrollment"}
• {"criterion_text":"- Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures"}
• {"criterion_text":"- Amyloid Light-chain (AL) amyloidosis"}
• {"criterion_text":"- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- Patients who are receiving any other investigational agents."}
• {"criterion_text":"- Concurrent systemic treatment or prior therapy within 4 weeks for SMM"}
• {"criterion_text":"- Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy"}
• {"criterion_text":"- History of allergic reactions attributed to immunomodulatory agents and proteasome inhibitors."}
• {"criterion_text":"- Hypersensitive reaction to active substances or any excipients of the IMPs"}
• {"criterion_text":"- Uncontrolled hypertension or diabetes"}
• {"criterion_text":"- Pregnant or lactating females."}

Primary endpoints

• {"endpoint_text":"- MRD negativity rate by NGF after cycle 9 for all eligible ITT patients; eligible patients who achieve a MRD negativity after cycle 9 will be considered as a success. All other eligible randomized ITT patients will be considered as a failure, including patients going off-protocol before cycle 9, whatever the cause.","definition_or_measurement_approach":"Measured by next generation flow (NGF) for MRD negativity after 9 cycles in all eligible intent-to-treat (ITT) patients; patients MRD-negative after cycle 9 are counted as success; others including those off-protocol before cycle 9 counted as failure."}

Secondary endpoints

• {"endpoint_text":"- MRD negativity rate evaluated by means of next generation flow cytometry (cut off 10-5) after cycle 4","definition_or_measurement_approach":"Measured by NGF at cutoff 10^-5 after 4 cycles"}
• {"endpoint_text":"- MRD negativity rate evaluated by means of next generation flow cytometry (cut off 10-5) after completion of maintenance","definition_or_measurement_approach":"Measured by NGF at cutoff 10^-5 after completion of maintenance"}
• {"endpoint_text":"- Correlation of MRD (NGF) negativity rate with PFS","definition_or_measurement_approach":"Correlation analysis between MRD negativity by NGF and progression-free survival (PFS)"}
• {"endpoint_text":"- Overall response rate (ORR; i.e. at least partial response (PR)) after 9 cycles induction treatment","definition_or_measurement_approach":"ORR defined as at least partial response after 9 cycles induction"}
• {"endpoint_text":"- Progression-free survival (PFS), defined as time from study entry to progression or death, whichever comes first","definition_or_measurement_approach":"Time-to-event endpoint measured from study entry to progression or death"}
• {"endpoint_text":"- Progression-free survival-2 (PFS2), defined at time from randomization to progression after second-line treatment or death, whichever comes first","definition_or_measurement_approach":"Time from randomization to progression after second-line treatment or death"}
• {"endpoint_text":"- Duration of response (DOR), defined as time from response to progression or death, whichever comes first","definition_or_measurement_approach":"Time from documented response to progression or death"}
• {"endpoint_text":"- Overall survival (OS), defined as time from study entry to death from any cause. Patients still alive at the date last contact will be censored","definition_or_measurement_approach":"Time from study entry to death from any cause; censoring at last contact for survivors"}
• {"endpoint_text":"- Correlation of MRD (NGF) negativity rate with PFS, PFS2, DOR and OS","definition_or_measurement_approach":"Correlation analyses between MRD negativity by NGF and multiple survival outcomes (PFS, PFS2, DOR, OS)"}
• {"endpoint_text":"- Toxicity of combination therapy (carfilzomib, lenalidomide, and dexamethasone)","definition_or_measurement_approach":"Evaluation of adverse events and toxicity related to combination therapy"}
• {"endpoint_text":"- Safety (type, frequency, and severity of adverse events (AE) and relationship of AE to study drug, serious AE (SAEs)","definition_or_measurement_approach":"Assessment of AEs and SAEs including type, frequency, severity, and relationship to study drug"}
• {"endpoint_text":"- Disease heterogeneity in relation to clinical outcomes (molecular profiling on bone marrow samples)","definition_or_measurement_approach":"Molecular profiling on bone marrow samples to assess disease heterogeneity and relation to clinical outcomes"}

Netherlands

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

02-09-2024

Processing Time Days

17

Number Of Sites

7

Number Of Participants

22

Norway

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

04-09-2024

Processing Time Days

19

Number Of Sites

1

Number Of Participants

36

Primary sponsor

Full Name

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"sponsorDuties code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"","full_name":"Amgen","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Celgene","duties_or_roles":"Monetary support","organisation_type":""}