Bortezomib, Lenalidomide and Dexamethasone Combination Therapy in Patients With Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of the bortezomib, lenalidomide and dexamethasone combination in patients with newly diagnosed multiple myeloma. We are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.

Detailed Description
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The safe dose of dexamethasone is already known. The dose of bortezomib and lenalidomide will be increased during the study until the best and safest amount (or dose) is identified. The participant's dose of the study drugs will depend on when they enter the study. In this study each cycle will be 21 days and participants will begin the study medication in the clinic on Cycle 1 Day 1. Lenalidomide (capsules) will be taken daily for the first 2 weeks only (Day 1-14). Dexamethasone (tablets) will be taken on Day 1, 2, 4, 5, 8, 9, 11 and 12. Bortezomib will be given intravenously in the outpatient treatment clinic on Day 1, 4, 8 and 11. The third week is a rest period and no study medication will be given. During the course of the study treatment, tests and procedures will be performed at designated time periods. This includes; medical history updates, physical/neurological examinations, skeletal survey (x-rays or scan), blood samples, optional bone marrow aspiration/tissue biopsy, urine samples, 12-lead ECG, and MRI/CT scan (if needed). It is expected that study participants will receive study treatment for 8 cycles (168 days). If the participant completes the first 8 cycles of the study, has stable or responding disease and has not experienced bad side effects, they will be allowed to continue treatment on a maintenance schedule, detailed in the protocol, at the study doctor's discretion.

Official Title
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An Open-Label Phase I/II Study of the Safety and Efficacy of Bortezomib, Lenalidomide and Dexamethasone Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Lenalidomide
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria Must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma Negative serum or urine pregnancy test Age 18 years or older Karnofsky performance status of greater or equal to 60 Exclusion Criteria: Greater or equal to Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment Renal insufficiency (serum creatinine >2.5 mg/dL) Evidence of mucosal or internal bleeding and/or platelet refractory ANC (absolute neutrophil count)< 1000 cells/mm3 Hemoglobin < 8.0 g/dL AST (aspartate aminotransferase) or ALT (alanine aminotransferase) greater than or equal to 2 x ULN (upper limit of normal) Concomitant therapy medications that include corticosteroids Myocardial infarction within 6 months prior to enrollment according to NYHA (New York Heart Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities Clinically relevant active infection or serious co-morbid medical conditions Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer Pregnant or breast-feeding Serious medical or psychiatric illness likely to interfere with participation in study Uncontrolled diabetes mellitus Hypersensitivity to acyclovir or similar anti-viral drug POEMS syndrome Known HIV infection Known active hepatitis B or C viral infection Known intolerance to steroid therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lenalidomide, dexamethasone, bortezomib combination<br>In this study each cycle will be 21 days and participants will begin the study medication in the clinic on Cycle 1 Day 1. Lenalidomide (capsules) will be taken daily for the first 2 weeks only (Day 1-14). Dexamethasone (tablets) will be taken on Day 1, 2, 4, 5, 8, 9, 11 and 12. Bortezomib will be given intravenously in the outpatient treatment clinic on Day 1, 4, 8 and 11. The third week is a rest period and no study medication will be given. | Drug: Bortezomib<br>* Intravenously on days 1, 4, 8 and 11 of a 21 day cycle for a minimum of 8 cycles (dosage will vary depending upon when the participant enters the trial)<br>Drug: Lenalidomide<br>* Taken orally twice a day for 2 weeks (days 1-14) of each 21-day cycle for a minimum of 8 cycles (dosage will vary depending upon when participant enters trial).<br>Drug: dexamethasone<br>* Taken orally on days 1,2,4,5,8,9,11 of a 21-day cycle for a minimum of 8 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate of the Drug Combination in This Patient Populations. | Overall Response (OR) was defined as partial response (PR) or better. Response was assessed according to European Group for Blood and Marrow Transplant criteria, modified to include nCR and VGPR, from the International Uniform Response Criteria. | Full response assessment was conducted at the end of cycle 8 (average of168 days) and after cycle 4 (84 days) for patients proceeding to transplant. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated 18-month Progression Free Survival (PFS) Rate | PD from European Bone Marrow Transplant (EBMT) Response Criteria Required one or more: >25% increased in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, or >25% increased in 24-hour urinary light chain excretion (must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation), or >25% increased in plasma cells in a bone marrow aspirate or biopsy (must also be an absolute increase of at least 10%) Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas. Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture). Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause). PFS was measured from treatment initiation to progression or death, censored at the date patients were last known to be alive and disease free | PFS rate at 18 months | 
| Percentage of Patients Who Remained in Response for More Than 18 Months | Duration of response was measured from first response to progression or death, censored at the date patients were last known to be alive and disease free for patients who had not progressed or died. | Response rate at 18 months | 
| Estimated 18-month Overall Survival Rate | Overall survival was measured from treatment initiation to death, censored at the date patients were last known to be alive for those who had not died. | Survival rate at 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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newly diagnosed multiple myeloma