Cyclosporine in Combination With Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma Refractory to Carfilzomib and High Expression of PPIA Gene in Myeloma Cells
- Conditions
- Multiple Myeloma, RefractoryMultiple Myeloma in Relapse
- Registration Number
- NCT04813653
- Lead Sponsor
- Tel-Aviv Sourasky Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br>Patients must meet all of the following inclusion criteria:<br><br> 1. Male or female patients, 18 years of age or older.<br><br> 2. Multiple myeloma diagnosed according to standard IMWG criteria.<br><br> 3. Patients must have measurable disease defined by at least one of the following three<br> measurements:<br><br> - Serum M-protein 1 g/dL (10 g/L).<br><br> - Urine M-protein 200 mg/24 hours.<br><br> - Serum free light chain assay: involved free light chain level at least 100<br> mg/L, provided that the serum free light chain ratio is abnormal.<br><br> 4. Patients received one or two prior lines of therapy which must have included<br> bortezomib, lenalidomide-and daratumumab.<br><br> 5. Patient received carfilzomib-based therapy either as their most recent line of<br> therapy and within 3 months from study enrolment, and either failed to achieve a<br> minor response after completing 2 cycles of carfilzomib based therapy, or are<br> refractory to treatment.<br><br> 6. Patients were found to have a high-expression level of PPIA, >1.2 unique RNA<br> molecules (UMI) per cell on average, by scRNA sequencing of their myeloma cells from<br> bone marrow aspiration sample at study screening.<br><br> 7. Patients must meet the following clinical laboratory criteria:<br><br> - Absolute neutrophil count (ANC) =1,000/mm3 and platelet count=75,000/mm3.<br> Platelet transfusions to help patients meet eligibility criteria are not<br> allowed within 3 days of enrolment.<br><br> - Total bilirubin =1.5 the upper limit of the normal range (ULN).<br><br> - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 ULN.<br><br> - Calculated creatinine clearance =45 mL/min<br><br> 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.<br><br> 9. Female patients who:<br><br> - Are postmenopausal for at least 24 months before the screening visit, OR<br><br> - Are surgically sterile, OR<br><br> - Who are of childbearing potential, and agree to practice two effective methods<br> of contraception (1 highly effective method and 1 additional effective method)<br> at the same time, from the time of signing the informed consent through 90 days<br> after the last dose of study treatment, OR agree to completely abstain from<br> heterosexual intercourse.<br><br> Females of childbearing potential (FCBP) must have a negative serum or urine<br> pregnancy test with a sensitivity of at least 25 milli International Units/mL within<br> 10 to 14 days of initiation of Cycle 1 and again within 24 hours of starting Cycle<br> 1. FCBP must also agree to ongoing pregnancy testing. All patients must be counseled<br> at a minimum of every 28 days about pregnancy precautions and risks of fetal<br> exposure.<br><br> 10. Male patients, even if surgically sterilized (i.e., status postvasectomy), who:<br><br> - Agree to completely abstain from heterosexual intercourse, OR<br><br> - Agree to practice effective barrier contraception (i.e., latex condom) during<br> sexual contact with a FCBP, even if they have had a successful vasectomy,<br> throughout the entire study treatment period and through 4 months after the<br> last dose of study treatment.<br><br> 11. Voluntary written consent must be given before performance of any study-related<br> procedure not part of standard medical care, with the understanding that consent may<br> be withdrawn by the patient at any time without prejudice to future medical care.<br><br> 12. Patient is willing and able to adhere to the study visit schedule and other protocol<br> requirements.<br><br> - Exclusion Criteria:<br><br> - Patients meeting any of the following exclusion criteria are not eligible to<br> participate in the study:<br><br> 1. Patient underwent an allogeneic transplantation.<br><br> 2. Major surgery within 14 days before enrolment.<br><br> 3. Central nervous system involvement<br><br> 4. Concomitant use of any other antineoplastic treatment with activity against MM<br> (with the exception of =40 mg Dexamethasone per day or equivalent for no longer<br> than 4 days).<br><br> 5. Anti-myeloma therapy as follows prior to screening bone marrow aspiration:<br><br> 1. Targeted therapy, within 14 days or at least 5 half-lives, whichever is<br> less;<br><br> 2. Monoclonal antibody treatment for multiple myeloma within 21 days;<br><br> 3. Cytotoxic therapy within 14 days;<br><br> 4. Proteasome inhibitor therapy within 14 days; note: no window is required<br> for carfilzomib<br><br> 5. Immunomodulatory agent therapy within 7 days.<br><br> 6. Radiotherapy within 14 days (with the exception of radiotherapy for spinal<br> cord compression or for pain control that should be discussed and approved<br> by the sponsor- investigator prior to study enrolment). However, if the<br> radiation portal covered =5% of the bone marrow reserve, the subject is<br> eligible irrespective of the end date of radiotherapy.<br><br> 6. Diagnosed or treated for another malignancy within 2 years before enrolment or<br> previously diagnosed with another malignancy and have any evidence of residual<br> disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type<br> are not excluded if they have undergone complete resection.<br><br> 7. Moderate to severe kidney injury (Calculated creatinine clearance =45 mL/min).<br><br> 8. Severe liver disease (cirrhosis grade Child-Pugh B or C; significant<br> hepatocellular or cholestatic liver injury).<br><br> 9. Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy,<br> organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes)<br> syndrome, plasma cell leukaemia, primary amyloidosis, myelodysplastic syndrome,<br> or myeloproliferative syndrome.<br><br> 10. Evidence of current uncontrolled cardiovascular conditions, including<br> uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic<br> congestive heart failure, unstable angina, or myocardial infarction within the<br> past 6 months.<br><br> 11. Psychiatric illness/social situation that would limit compliance with study<br> requirements.<br><br> 12. Patient with a known diagnosis of Epilepsy.<br><br> 13. Known allergy to any of the study medications, their analogues, or excipients<br> in the various formulations of any agent.<br><br> 14. Comorbid systemic illnesses or other severe concurrent disease which, in the<br> judgment of the investigator, would make the patient inappropriate for entry<br> into this study or interfere significantly with the proper assessment of safety<br> and toxicity of the prescribed regimens.<br><br> 15. Systemic treatment with strong inhibitors of Cytochrome P450 family 3,<br> subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole,<br> ketoconazole, nefazodone, posaconazole) or strong Cytochrome P450 (CYP3A),<br> family 3, subfamily A inducers (rifampin, rifapentine, rifabutin,<br> carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's<br> wort within 14 days before enrolment in the study.<br><br> 16. Infection requiring systemic antibiotic therapy or other serious infection
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment parameters.
- Secondary Outcome Measures
Name Time Method Overall response rate ORR;Progression free survival PFS;Duration of Response DOR;Time to Response TTR;Depth of Best Response (DpR);Time to progression (TTP);Overall Survival (OS);Extramedullary progression;Extramedullary progression;Percentage of cyclosporine trough levels tests in acceptable range;Mean % of levels in acceptable range will be calculated for the efficacy population.