Randomized Phase II Study in Elderly Patients With Newly Diagnosed Multiple.

Study Purpose

To compare the efficacy and safety of bortezomib, lenalidomide and dexamethasone in elderly frail patients with newly diagnosed multiple myeloma. 1. Primary Study Objective.

- Progression-Free Survival.

: The time from randomization into the date of first observation of documented disease progression or any-kinds of death. 2. Secondary Study Objectives 1) Complete Response (CR)

- Response will be determined by the International Myeloma Working Group Response Criteria.

- CR is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytoma and < 5% of plasma cells in bone marrow aspirates.

- The determination of stringent CR and Imaging will be done 2) Overall response rate consisting of complete response, very good partial response, and partial response 3) Overall survival (OS) - The time from randomization into the date of any-kinds of death.

4) Time to next treatment.

- The time from randomization into the first date of second-line treatment.

5) Toxicity profiles

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	70 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Newly diagnosed with multiple myeloma. 2. Older than 70 years. 3. Ineligible for autologous stem cell transplantation. 4. No history of prior treatment for multiple myeloma. 5. At least one of the following measuarble disease.

- Serum M-protein ≥ 0.5 g/dL, or urine M-protein ≥ 200mg/24 hour, or.

- In patients without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lambda ratio.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. 7. Adequate hepatic functionwith bilirubin < 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN. 8. Left ventricular ejection fraction (LVEF) ≥ 40%. 9. Absolute neutrophil count (ANC) ≥ 1000/mm³: Screening ANC should be independent of growth factor support for ≥ 1 week. 10. Hemoglobin ≥ 8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell transfusions is allowed); Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ -if myeloma involvement in the bone marrow is >50%): Patients should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count. 11. Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min.

- Calculation should be based on standard formula such as the Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female.

12. Written informed consent in accordance with institutional guidelines. 13. Female patients of child-bearing potential (FCBP) must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to starting lenalidomide. The first pregnancy test must be performed within 10 to 14 days prior to the start of lenalidomide and the second pregnancy test must be performed within 24 hours prior to the start of lenalidomide. Effective method of contraception should be used during and for 28 days following last dose of drug.

- FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

14. Male patients must use an effective barrier method of contraception during study and for 28 days following the last dose if sexually active with a FCBP.

Exclusion Criteria:

1. Relapsed or refractory multiple myeloma. 2. Multiple Myeloma of IgM subtype. 3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). 4. Plasma cell leukemia or circulating plasma cells ≥ 2 × 10^9/L. 5. Waldenstrom's Macroglobulinemia. 6. Patients with known amyloidosis. 7. Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to the 1st day of 1st cycle. 8. Focal radiation therapy within 7 days prior to the 1st day of 1st cycle. 9. Immunotherapy within 21 days prior to the 1st day of 1st cycle. 10. Major surgery (excluding kyphoplasty) within 28 days prior to 1st day of 1st cycle. 11. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to 1st day of 1st cycle. 12. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to 1st day of 1st cycle. 13. Known human immunodeficiency (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed). 14. Patients with known cirrhosis. 15. Female patients who are pregnant or lactating. 16. Patients with contraindication to dexamethasone. 17. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment. 18. Patients with end-stage renal disease requiring hemodialysis or peritoneal dialysis

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04277845
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Samsung Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Multiple Myeloma

Additional Details

Group 1: 1 cycle will be repeated every 4 weeks. 1. Bortezomib 1.3mg/m2 SC D1, 8, 15.

- Dose adjustment for more than 85 : 1.0mg/m2 SC D1, 8, 15.

2. Lenalidomide 25mg/d D1-21. 3. Dexamethasone 40mg D1, 8, 15

- Dose adjustment for more than 75 years old: 20mg If it is difficult to maintain bortezomib due to unacceptable toxicity, it can early discontinue from Group 1.

If a patient is frail, the starting dosage will be as follows. 1. Bortezomib 1.0mg/m2 SC D1, 8, 15.

- Dose adjustment for more than 85 : 1.0mg/m2 SC D1,8,15.

2. Lenalidomide 15mg/d D1-21. 3. Dexamethasone 40mg D1, 8, 15

- Dose adjustment for more than 75: 20mg.

Group 2: 1 cycle will be repeated every 4 weeks. 1. Lenalidomide 25mg/d D1-21. 2. Dexamethasone 40mg D1, 8, 15, 22

- Dose adjustment for more than 75: 20mg.

If a patient is frail in both study group, the starting dosage will be as follows. 1. Lenalidomide 15mg/d D1-21. 2. Dexamethasone 40mg D1, 8, 15

- Dose adjustment for more than 75: 20mg .

Arms & Interventions

Arms

Experimental: Group 1

Bortezomib 1.3mg/m2 SC D1, 8, 15 - Dose adjustment for more than 85 : 1.0mg/m2 SC D1, 8, 15 Lenalidomide 25mg/d D1-21 Dexamethasone 40mg D1, 8, 15 Dose adjustment for more than 75 years old: 20mg If it is difficult to maintain bortezomib due to unacceptable toxicity, it can early discontinue from Group 1. If a patient is frail, the starting dosage will be as follows. Bortezomib 1.0mg/m2 SC D1, 8, 15 - Dose adjustment for more than 85 : 1.0mg/m2 SC D1,8,15 Lenalidomide 15mg/d D1-21 Dexamethasone 40mg D1, 8, 15 Dose adjustment for more than 75: 20mg

Active Comparator: Group 2

Lenalidomide 25mg/d D1-21 Dexamethasone 40mg D1, 8, 15, 22 Dose adjustment for more than 75: 20mg If a patient is frail in both study group, the starting dosage will be as follows. Lenalidomide 15mg/d D1-21 Dexamethasone 40mg D1, 8, 15 Dose adjustment for more than 75: 20mg .

Interventions

Drug: - Renalidomide, Velcade, Dexamethasone

Multiple Myeloma M-Proteins

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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