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

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 1
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 newly diagnosed multiple myeloma

Eligibility Criteria

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

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

Sites / Locations

  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

lenalidomide, dexamethasone, bortezomib combination

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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.

Full Information

First Posted
September 18, 2006
Last Updated
April 18, 2023
Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Celgene Corporation, Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00378105
Brief Title
Bortezomib, Lenalidomide and Dexamethasone Combination Therapy in Patients With Newly Diagnosed Multiple Myeloma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 2006 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
lenalidomide, dexamethasone, bortezomib combination
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
Taken orally on days 1,2,4,5,8,9,11 of a 21-day cycle for a minimum of 8 cycles.
Primary Outcome Measure Information:
Title
Objective Response Rate of the Drug Combination in This Patient Populations.
Description
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.
Time Frame
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 Measure Information:
Title
Estimated 18-month Progression Free Survival (PFS) Rate
Description
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
Time Frame
PFS rate at 18 months
Title
Percentage of Patients Who Remained in Response for More Than 18 Months
Description
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.
Time Frame
Response rate at 18 months
Title
Estimated 18-month Overall Survival Rate
Description
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.
Time Frame
Survival rate at 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
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
25824111
Citation
Dytfeld D, Rosebeck S, Kandarpa M, Mayampurath A, Mellacheruvu D, Alonge MM, Ngoka L, Jasielec J, Richardson PG, Volchenboum S, Nesvizhskii AI, Sreekumar A, Jakubowiak AJ. Proteomic profiling of naive multiple myeloma patient plasma cells identifies pathways associated with favourable response to bortezomib-based treatment regimens. Br J Haematol. 2015 Jul;170(1):66-79. doi: 10.1111/bjh.13394. Epub 2015 Mar 30.
Results Reference
derived
PubMed Identifier
20385792
Citation
Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. doi: 10.1182/blood-2010-02-268862. Epub 2010 Apr 12.
Results Reference
derived

Learn more about this trial

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

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