Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and side effects of the bortezomib, lenalidomide and dexamethasone combination in relapsed or relapsed and refractory multiple myeloma. Each of these drugs are approved by the U.S Food and Drug Administration, but have not been approved in the combination for treating patients in this setting.

Detailed Description
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Participants took the study medication in the clinic on Cycle 1 day 1. Each treatment cycle lasted three weeks. They took the lenalidomide (capsules) every day for the first two weeks only (days 1-14). They took dexamethasone (tablets) on Day 1, 2, 4, 5, 8, 9, 11 and 12 and came to the outpatient treatment center for intravenous bortezomib on Day 1, 4, 8 and 11. The third week of the cycle was a rest period and the participant did not take any study medication. Certain tests and procedures were performed throughout each treatment cycle at definitive time periods. These tests included: medical history update, physical/neurological examination, skeletal survey (x-rays or scan), blood samples, urine samples, optional bone marrow aspiration/tissue biopsy, 12-lead ECG, and MRI/CT (if needed). It was expected that participants were going to complete at least 8 cycles of the study, which adds up to 168 days. If the participant completed the first 8 cycles, had stable or responding disease and had not experienced bad side effects, they were allowed to continue treatment on a maintenance schedule, detailed in the protocol, at the study doctor's discretion.

Official Title
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Am Open-Label Phase II Study of the Safety and Efficacy of Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory 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: Diagnosis of multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria Relapsed or relapsed and refractory disease after receiving between 1 and 3 prior regimens Negative serum or urine pregnancy test Age 18 years or older Karnofsky performance status of 60 or greater Exclusion Criteria: Grade 2 or greater peripheral neuropathy within 14 days before enrollment Renal insufficiency (serum creatinine > 2.5 mg/dL) Evidence of mucosal or internal bleeding and/or platelet refractory ANC < 1000 cells/mm3 Hemoglobin < 8.0 g/dL AST or ALT greater than or equal to 2 x ULN Concomitant therapy medications that include corticosteroids Myocardial infarction within 6 months prior to enrollment or has NYHA 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 (within last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, in situ prostate cancer Pregnant or breast-feeding Serious medical or psychiatric illness likely to interfere with participation in this clinical 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 Subjects with primary refractory disease, defined as progression during initial treatment

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>Participants took the study medication in the clinic on Cycle 1 day 1. Each treatment cycle lasted three weeks. They took the lenalidomide (capsules) every day for the first two weeks only (days 1-14). They took the dexamethasone (tablets) on Day 1, 2, 4, 5, 8, 9, 11 and 12 and came to the outpatient treatment center for intravenous bortezomib on Day 1, 4, 8 and 11. The third week of the cycle was a rest period and the participant did not take any study medication. | Drug: Bortezomib<br>* Given intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles.<br>Drug: Lenalidomide<br>* Taken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles<br>Drug: Dexamethasone<br>* Taken orally on days 1,2,4,5,8,9,11,and 12 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 |
| --- | --- | --- |
| The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months | Response assessed by the European Group for Blood and Marrow Transplant (EBMT) criteria, modified to include nCR and VGPR from the international uniform response criteria (IMWG). Progressive disease (PD) required one or more of the following: >25% increased in serum monoclonal paraprotein (must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation) >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) >25% increased in plasma cells in a bone marrow aspirate or on trephine 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). | 6 months after therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Response assessed by the European Group for Blood and Marrow Transplant (EBMT) criteria, modified to include nCR and VGPR from the international uniform response criteria (IMWG). Objective response was defined by the achievement of at least Partial Response (PR) or better (CR-complete response, nCR-near complete response, and VGPR-very good partial response). | Assessed every cycle for up to 8 cycles and best response was reported | 
| Duration of Response | Duration of response will be measured as the time from initiation of a response to first documentation of disease progression or death, or date last known progression-free and alive for those who have not progressed or died. | Assessed at a median follow-up of 44 months | 
| Progression Free Survival | Progression-free survival is defined as the time from registration to the disease progression or death from any cause, censored at date last known progression-free for those who have not progressed or died. | aassesed at a median follow-up of 44 months | 
| Overall Survival | defined as time from treatment initiation to death, or last known to be alive for those who had not died | assesed at a median follow-up of 44 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed multiple myeloma, refractory multiple myeloma