POMALIDOMIDE for Smoldering multiple myeloma (high risk of progression to symptomatic myeloma)

Inclusion criteria

• {"criterion_text":"- •\tThe patient must, in the investigator’s opinion, be able to fulfill all of the clinical trial requirements."}
• {"criterion_text":"- •\tThe patient must voluntarily sign the informed consent document before any study procedures that are not part of standard clinical care are carried out. The patient must be made aware that they can withdraw from the study at any time without this affecting their future medical care."}
• {"criterion_text":"- •\tThe patient must be aged between 18 and 70 years, and eligible to receive high-dose therapy and autologous peripheral blood stem cell transplant."}
• {"criterion_text":"- •\tThe patient must have been diagnosed with SMM with high risk of progression to symptomatic MM, or ultra-high risk of progression to symptomatic disease in the five years prior to inclusion in the study. It should be emphasized that we are referring to a diagnosis of high-risk SMM during this time period, not to monoclonal gammopathy, or intermediate or low-risk smoldering myeloma. In other words: o\tSMM with high risk of progression to symptomatic disease: 1.\t≥ 10% BM clonal PC and presence of a monoclonal protein, IgG >3 g/dl or IgA >2 g/dl or Bence Jones proteinuria of >1 g/24h and absence of lytic lesions, hypercalcemia, renal failure (creatinine < 2 mg/dl) and anemia (hemoglobin > 10 g/dl, or not 2 g/dl below the lower limit of normal.) 2.\t≥ 10% BM clonal PC or IgG >3 g/dl or IgA >2 g/dl, or Bence Jones proteinuria > 1 g/24 h (but not both at the same time), always in the absence of lytic lesions, hypercalcemia, renal failure and anemia. These patients can be included in the study if they fulfill the following additional criteria: -\tPresence of a percentage of phenotypically abnormal PC in the in plasma cell compartment of the BM (aPC/PC) ≥ 95% and immunoparesis, defined as a reduction in the concentration of 1 or 2 immunoglobulins (lgs) by more the 25%, compared with the normal values of the corresponding lg. o\tSMM with ultra-high risk of progression to symptomatic disease: 1.\tAppearance of more than 1 focal lesion on MRI (ideally whole-body MRI) 2.\tClonal PC in BM ≥ 60%. 3.\tRatio of involved /uninvolved sFLC greater than 100 together with involved free light chain levels great than 100 mg/L."}
• {"criterion_text":"- •\tThe patient must present an ECOG performance status of < 2."}
• {"criterion_text":"- •\tThe patient must be able to attend scheduled visits."}
• {"criterion_text":"- •\tWomen with gestational capacity must have a negative pregnancy test (serum or urine) which will be taken in the 14 days prior to initiation of treatment with the study drug. Sexually active women must also agree to use two methods of contraception [hormonal contraceptives (oral, injectable, or implants)], tubal ligation, intrauterine device, barrier methods with spermicide, or her partner has had a vasectomy) while receiving the study drug. Women with gestational capacity must agree to have a pregnancy test every 4 weeks (urine or serum) while receiving the study drug (or every 14 days if they have irregular menstrual cycles), and 4 weeks after receiving the last dose of the study drug."}

Exclusion criteria

• {"criterion_text":"- •\tAny physical or mental health condition that prevents the patient from signing or understanding the informed consent document."}
• {"criterion_text":"- •\tThe patient has received prior treatment for SMM."}
• {"criterion_text":"- •\tThe patient is pregnant or breastfeeding."}
• {"criterion_text":"- •\tThe patient has lytic lesions, anemia, renal failure or hypercalcemia."}
• {"criterion_text":"- •\tAny of the following abnormal laboratory values: o\tAbsolute neutrophil count (ANC) < 1,000/mm3. o\tPlatelet count < 75,000/mm3. o\tSerum GOT or GPT > 3 times the upper limit of normal. o\tTotal serum bilirubin > 2 times the upper limit of normal."}
• {"criterion_text":"- •\tHistory of neoplasms other than multiple myeloma (except in the case of basal cell skin cancers, squamous cell cancers or carcinoma in situ of the cervix or breast unless the patient has been disease-free for >5 years."}
• {"criterion_text":"- •\tThe patient has undergone major surgery in the 4 weeks prior to inclusion in the study."}
• {"criterion_text":"- •\tThe patient has active HIV, hepatitis B or hepatitis C infection."}
• {"criterion_text":"- •\tThe patient has received an investigational drug of any type in the 4 weeks prior to inclusion in the study."}
• {"criterion_text":"- •\tThe patient has experienced unstable angina or myocardial infarction in the 6 months prior to recruitment, class III or IV cardiac failure (according to the New York Heart Association criteria) uncontrolled angina, a history of acute coronary artery syndrome, uncontrolled ventricular arrhythmias, sick sinus syndrome or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities, unless the patient has a pacemaker."}
• {"criterion_text":"- •\tUncontrolled hypertension or diabetes."}
• {"criterion_text":"- •\tSignificant neuropathy (grades 3-4, or grade 2 with pain), in the 14 days prior to recruitment."}
• {"criterion_text":"- •\tKnown history of allergies to captisol (a derivative of cyclodextrin that is used to dissolve carfilzomib)."}
• {"criterion_text":"- •\tThe patient presents a contraindication that prevents the administration of the concomitant or adjunctive treatments, including hydration intolerance due to pre-existing pulmonary or cardiac impairment."}
• {"criterion_text":"- •\tLVEF < 40"}
• {"criterion_text":"- •\tPulmonary hypertension."}

Primary endpoints

• {"endpoint_text":"- •\tImmunophenotypic complete remission (CR by flow cytometry) day +100 after induction treatment and HDT-ASCT.","definition_or_measurement_approach":"Assessed by multiparametric flow cytometry (MFC) to determine immunophenotypic complete response (CR) with MRD-negative status on day +100 after high-dose therapy and autologous stem cell transplantation."}

Secondary endpoints

• {"endpoint_text":"- •\tImmunophenotypic complete remission (CR by flow cytometry), after consolidation and maintenance, and at 3 and 5 years post-HDT-ASCT.","definition_or_measurement_approach":"Assessed by multiparametric flow cytometry (MFC) for immunophenotypic CR (MRD status) after consolidation and maintenance and at 3- and 5-year timepoints."}
• {"endpoint_text":"- •\tResponse rates (sCR, CR, VGPR and ORR) after the different phases of treatment (induction, HDT-ASCT, consolidation, maintenance and rescue therapy).","definition_or_measurement_approach":"Response rates defined by standard multiple myeloma response categories: sCR, CR, VGPR and ORR after each treatment phase (specific assessment methods not detailed here)."}
• {"endpoint_text":"- •\tTTP to symptomatic disease, PFS and OS.","definition_or_measurement_approach":"Time-to-event endpoints: time to progression (TTP) to symptomatic disease, progression-free survival (PFS) and overall survival (OS) as measured from defined study timepoints (specific censoring rules not provided in the available data)."}
• {"endpoint_text":"- •\tSafety profile after the different phases of treatment: induction, high-dose melphalan treatment and autologous hematopoietic stem cell transplantation, consolidation, maintenance and rescue therapy.","definition_or_measurement_approach":"Safety assessed by collection and reporting of adverse events and other safety measures during each study phase (detailed safety assessment methods not provided in the available data)."}

Spain

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

23-10-2024

Processing Time Days

1

Number Of Sites

20

Number Of Participants

90

Primary sponsor

Full Name

Fundacion PETHEMA

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Farmavenix S.A.","duties_or_roles":"[{\"id\":816629,\"code\":\"14\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"[{\"id\":816630,\"code\":\"14\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Hospital Universitario 12 De Octubre","duties_or_roles":"[{\"id\":816627,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Clinica Universidad De Navarra","duties_or_roles":"[{\"id\":816626,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Evidenze Health Espana S.L.","duties_or_roles":"[{\"id\":816621,\"code\":\"1\"},{\"id\":816622,\"code\":\"12\"},{\"id\":816623,\"code\":\"14\"},{\"id\":816624,\"code\":\"5\"},{\"id\":816625,\"code\":\"8\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Hospital Universitario De Salamanca","duties_or_roles":"[{\"id\":816628,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}