Multiple MyelomaPhase 2NCT00378209
Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma
A Phase 2 study testing Bortezomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Bortezomib, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2006to Oct 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
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
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib, Lenalidomide, Dexamethasone
- Keywords
- relapsed multiple myeloma, refractory multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Given intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles.
LenalidomideDrug
Taken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles
DexamethasoneDrug
Taken orally on days 1,2,4,5,8,9,11,and 12 of a 21-day cycle for a minimum of 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| lenalidomide, dexamethasone, bortezomib combination | Experimental | 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. Receives: Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months after therapy
Secondary outcomes (4)
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).
Measured: 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.
Measured: 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.
Measured: 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
Measured: assesed at a median follow-up of 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2006 (estimated)
- Study startAug 2006
- Primary completionOct 2012
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Celgene Corporation, Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Paul G. Richardson, MD, Dana-Farber Cancer Institute
- Investigators
- Paul Richardson, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00378209
- Sponsor's protocol ID
- 06-147
- Status last verified
- Oct 2016
- First submitted
- 18 Sep 2006
- Last updated
- 17 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 24429336
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00378209
- Acronym / sponsor ID
- 06-147
- Conditions
- Multiple Myeloma
- Keywords
- relapsed multiple myeloma, refractory multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Celgene Corporation, Millennium Pharmaceuticals, Inc.
- Study start
- Aug 2006
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 19 Sep 2006 (estimated)
- Results
- Posted 9 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lenalidomide, dexamethasone, bortezomib combination | Experimental | Drug: Bortezomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibGiven intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles. | Drug | lenalidomide, dexamethasone, bortezomib combination |
| LenalidomideTaken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles | Drug | lenalidomide, dexamethasone, bortezomib combination |
| DexamethasoneTaken orally on days 1,2,4,5,8,9,11,and 12 of a 21-day cycle for a minimum of 8 cycles | Drug | lenalidomide, dexamethasone, bortezomib combination |
Primary outcome
The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months
Time frame: 6 months after therapy
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).
4 secondary outcomes
Objective Response Rate
Time frame: Assessed every cycle for up to 8 cycles and best response was reported
Duration of Response
Time frame: Assessed at a median follow-up of 44 months
Progression Free Survival
Time frame: aassesed at a median follow-up of 44 months
Overall Survival
Time frame: assesed at a median follow-up of 44 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24429336Richardson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Richardson, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months (time frame: 6 months after therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00378209, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2016.