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

Phase 1

Active, not recruiting

Conditions: Multiple Myeloma

Interventions: Drug: Bortezomib
Drug: Lenalidomide
Drug: dexamethasone

Registration Number: NCT00378105

Lead Sponsor: Dana-Farber Cancer Institute

Brief Summary: 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: * 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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 68

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
lenalidomide, dexamethasone, bortezomib combination	Bortezomib	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.
lenalidomide, dexamethasone, bortezomib combination	Lenalidomide	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.
lenalidomide, dexamethasone, bortezomib combination	dexamethasone	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate of the Drug Combination in This Patient Populations.	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.	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.

Secondary Outcome Measures

Name	Time	Method
Estimated 18-month Progression Free Survival (PFS) Rate	PFS rate at 18 months	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
Percentage of Patients Who Remained in Response for More Than 18 Months	Response rate at 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.
Estimated 18-month Overall Survival Rate	Survival rate at 18 months	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.

Trial Locations

Locations (3): Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States