Newly diagnosed multiple myeloma
Conditions
Interventions
Trade Name: Revlimid
Product Name: Revlimid
Pharmaceutical Form: Capsule, hard
Trade Name: Velcade
Product Name: Velcade
Pharmaceutical Form: Powder and solution for solution for injection
Trade N
Sponsors
Cancer Trials Ireland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must have a diagnosis of MM according Revised International Myeloma Working Group diagnostic criteria (Rajkumar 2014): Clonal bone marrow plasma cells =10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: •?End organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: - Hypercalcaemia: serum calcium >0·25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2·75 mmol/L (>11 mg/dL) - Renal insufficiency: creatinine clearance 177 µmol/L (>2 mg/dL) - Anemia: hemoglobin value of >20 g/L below the lower limit of normal,or a hemoglobin value 1 focal lesions on MRI studies 2. Patient has received no prior treatment with any systemic therapy for the treatment of multiple myeloma. a. Prior treatment of hypercalcaemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period) b. Bisphosphonates are permitted c. Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. Two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and 2 weeks have passed since the last date of therapy. 3. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 4. Age = 18 years at the time of signing Informed Consent. 5. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Lenalidomide Pregnancy Prevention Risk Management Plan. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mlU/mL 10 to14 days prior to therapy and repeated again within 24 hours prior to prescribing lenalidomide for induction Cycle 1 (prescriptions must be filled within 7 days as required by Lenalidomide Pregnancy Prevention Risk Management Plan) and must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must practice complete abstinence or agree to use a condom during sexual contact with a FCBP even if they have had a successful vasectomy. All study participants must be registered into the mandatory Lenalidomide Pregnancy Prevention Risk Management Plan, and be willing and able to comply with the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan. *A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy (the urgical remova
Exclusion criteria
Exclusion criteria: 1. Patient has = Grade 2 peripheral neuropathy on clinical examination within 14 days before enrolment 2. Renal insufficiency (serum creatinine levels > 2.5 mg/dL/221µmol/L, calculated creatinine clearance with Cockcroft-Gault formula (see Appendix G) 2 x ULN, bilirubin levels 1.5 ULN 7. Concomitant therapy medications that include corticosteroids (except as indicated in inclusion criteria) 8. Myocardial infarction within 6 months prior to enrolment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix G), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities 9. Clinically relevant active infection requiring treatment (antibiotics, antivirals, antifungals) 10. Any serious co-morbid condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. 11. Female subject is pregnant or breast-feeding 12. Serious psychiatric illness or addiction likely to interfere with participation in this clinical study 13. Uncontrolled diabetes mellitus 14. Contraindication to any required concomitant drugs or supportive therapies including hypersensitivity to all anticoagulation and antiplatelet options or hypersensitivity to acyclovir or similar anti-viral drug. History of allergic reaction/hypersensitivity attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dehydrate 15. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes) 16. Known seropositive for or active HIV infection active hepatitis B or C viral infection. Patients who are seropositive because of hepatitis B virus vaccine are eligible 17. Known intolerance to steroid therapy 18. Patient has hypersensitivity to bortezomib, boron, or mannitol 19. Diagnosed or treated for another malignancy within 2 years of enrolment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy 20. Participation in clinical trials with other anti-myeloma investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial 21. Radiation therapy within 2 weeks before randomization. Enrolment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the overall response rate after 4 cycles and the best response to induction therapy with combination of lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.;Secondary Objective: i. To evaluate the rate and severity of Peripheral Neuropathy (PN) of SQ bortezomib in combination with lenalidomide, and dexamethasone after the 4th and after the final cycle of induction therapy ii. To evaluate safety of induction therapy iii. To evaluate safety of maintenance therapy iv. To evaluate Time To Progression (TTP) v. To evaluate Progression-Free Survival (PFS) vi. To evaluate duration of response vii. To evaluate Overall Survival (OS). Exploratory Objectives: For patients who elect to go on to stem cell transplant, exploratory endpoints will also be stem cell yield (number of CD34+ cells and days of harvesting) and engraftment parameters. ;Primary end point(s): The most clinically relevant endpoint for this multiple myeloma population is overall response rate (ORR).;Timepoint(s) of evaluation of this end point: After 4 cycles of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): i. Peripheral neuropathy (PN). ii. Safety. iii. Time to progression (TTP). iv. Progression-free survival (PFS). v. Duration of response. vi. Overall survival (OS). ;Timepoint(s) of evaluation of this end point: i. PN: after 4th and after final induction treatment cycle. ii. Safety: end of each treatment cycle and up to 30 days post last dose of study drug. iii. TTP: time from registration to progression, censored at date last known to be progression-free or at time of death. iv. PFS: time from registration to disease progression or death from any cause, censored at date last known to be progression-free for those who have not progressed or died. v. Duration of response: time from first response after treatment to date of disease progression or death from any cause, or date last known progression-free and alive. vi. OS: time from registration to death from any cause or date last known alive for those who have not died. | — |
Countries
Ireland
Contacts
Public ContactClinical Trials Information
Cancer Trials Ireland
Outcome results
None listed