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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Lenalidomide
Dexamethasone
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring relapsed multiple myeloma, refractory multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

lenalidomide, dexamethasone, bortezomib combination

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
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.
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.
Overall Survival
defined as time from treatment initiation to death, or last known to be alive for those who had not died

Full Information

First Posted
September 18, 2006
Last Updated
October 18, 2016
Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Massachusetts General Hospital, Celgene Corporation, Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00378209
Brief Title
Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Massachusetts General Hospital, Celgene Corporation, Millennium Pharmaceuticals, Inc.

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
relapsed multiple myeloma, refractory multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
lenalidomide, dexamethasone, bortezomib combination
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
Given intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Taken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Taken orally on days 1,2,4,5,8,9,11,and 12 of a 21-day cycle for a minimum of 8 cycles
Primary Outcome Measure Information:
Title
The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months
Description
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).
Time Frame
6 months after therapy
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
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).
Time Frame
Assessed every cycle for up to 8 cycles and best response was reported
Title
Duration of Response
Description
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.
Time Frame
Assessed at a median follow-up of 44 months
Title
Progression Free Survival
Description
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.
Time Frame
aassesed at a median follow-up of 44 months
Title
Overall Survival
Description
defined as time from treatment initiation to death, or last known to be alive for those who had not died
Time Frame
assesed at a median follow-up of 44 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Richardson, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24429336
Citation
Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. doi: 10.1182/blood-2013-07-517276. Epub 2014 Jan 15.
Results Reference
derived

Learn more about this trial

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

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