Multiple MyelomaPhase 2NCT00441168
Velcade (Bortezomib), Adriamycin Dexamethasone (PAD) or Vincristine Adriamycin Dexamethasone in Second Line Treatment of Multiple Myeloma
A Phase 2 study testing adriamycin, bortezomib and dexamethasone in people with Multiple Myeloma, run by Janssen-Cilag International NV at 16 sites in 7 countries.
Trial summary
The purpose of this research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in… 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?
- adriamycin, bortezomib and dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 16 sitesin 7 countries
- Study dates
- Dec 2006to Jan 2008
- 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
- Relapsed or refractory multiple myeloma following 1 previous line of therapy and, is scheduled by the investigator to be treated with vincristine, adriamycin and dexamethasone standard therapy
- measurable secretory multiple myeloma based on defined criteria
- Karnofsky performance status of >or = 60%
- fulfils defined laboratory requirements within 14 days before baseline
- if female, the patient is either postmenopausal or surgically sterilised or willing to use an acceptable method of birth control for defined period of time
- if male, the patient agrees to use an acceptable barrier method for contraception for a defined period of time.
Who cannot join
- More than one previous line of therapy for multiple myeloma
- use of bortezomib in the previous line of therapy and/or received bortezomib in a previous trial
- known allergy or hypersensitivity to bortezomib, boron or mannitol
- peripheral neuropathy or neuropathic pain of grade 2 or higher
- myocardial infarction within 6 months of enrollment or had New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
Trial locations and contacts
16 sites in 7 countries.
16 sites in 7 countries
Turkey (Türkiye)3 sites
Study site
Ankara
Study site
Bursa
Study site
Eskişehir
About this study
Official title: A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Velcade When Added to Adriamycin-Dexamethasone Treatment Versus Vincristine-Adriamycin-Dexamethasone Standard Treatment in Subjects With Multiple Myeloma Who Are Refractory to or Have Relapsed After Primary Therapy for Multiple Myeloma
The purpose of this research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in patients with multiple myeloma. Multiple Myeloma is the second most common cancer of the blood. Bortezomib is the first approved cancer treatment in a new class of medicines called proteasome inhibitors. It disrupts the cell cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells. The treatment will be used as second line treatment, which means either the disease has returned after a period of improvement (relapse) or the disease did not respond to the initial treatment (refractory). Patients will receive either bortezomib (PS341), doxorubicin (Adriamycin) and dexamethasone (PAD) or the VAD standard therapy.
Read the detailed description
Bortezomib, has been approved for use in patients with multiple myeloma, who have already received at least one prior treatment and whose disease is worsening on their last treatment and who have already undergone or are unsuitable for bone marrow transplantation. Bortezomib has significant activity in patients with relapsed multiple myeloma, its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin. The VAD combination has been widely used in multiple myeloma and has demonstrated to be effective in relapsed patients. Based on previous trial results, it is hoped that bortezomib, in replacing vincristine in the VAD standard therapy, can improve the response to treatment of patients with multiple myeloma, with manageable side effects. This is an international, multicentre, randomised, open-label, parallel group study. About 212 patients will take part in the study. Patients will be treated with either bortezomib (PS-341), Adriamycin and Dexamethasone (PAD) or Vincristine, Adriamycin and Dexamethasone (VAD). There will be an initial 14 day screening period to evaluate if the patient is suitable for the study. After screening, eligible patients will be randomised to receive either PAD or VAD. Patients will receive therapy for up to 8 treatment cycles of 28 days each. After the treatment period, there will be a long-term follow-up period with monthly visits until disease progression or relapse. Thereafter follow-up will be continued by at least a phone call every other month. This long-term follow-up period will be performed for all patients until the last patient was treated and followed up for 1 year. Response to treatment will be assessed according to the European group for blood and marrow transplant criteria (EBMT). Disease burden will be monitored by measuring M-protein concentration in serum and in urine every 4 weeks until disease progression or relapse. Thereafter follow-up for survival will be continued every other month by at least a phone call. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examination and clinical laboratory tests. Treatment with PAD or VAD will be for up to 8 cycles of 28 days each. Treatment beyond 6 cycles will be discussed on individual basis. Proposed dosages are: bortezomib 1.3 mg/m² intravenous (IV) bolus on Days 1, 4, 8, and 11; vincristine 0.4mg IV push on Days 1 to 4; doxorubicin 9mg/m² IV push on Days 1 to 4; dexamethasone in 1st cycle 40 mg daily on Days 1 to 4, 9 to 12 and 17 to 20, orally (or equivalent parenteral dose) and on subsequent cycles as 40 mg daily on Days 1 to 4 and 17 to 20 only.
- Conditions
- Multiple Myeloma
- Being tested
- adriamycin, bortezomib, dexamethasone, vincristine
- Keywords
- Multiple Myeloma, bortezomib, Cancer, Hematology, bone marrow, immunoglobulin, relapse, refractory, plasma cell, Velcade, adriamycin, dexamethasone, vincristine
- Medical subject headings
- Multiple Myeloma, Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adriamycinDrug
adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4
bortezomibDrug
bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11
dexamethasoneDrug
dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
vincristineDrug
vincristine: 0.4mg IV push on days 1 to 4
| Study group | Role | What they receive |
|---|---|---|
| VAD Treatment | Active comparator | vincristine in combination with adriamycin and dexamethasone Receives: Drug: adriamycin; Drug: dexamethasone; Drug: vincristine |
| PAD Treatment | Experimental | bortezomib in combination with adriamycin and dexamethasone Receives: Drug: adriamycin; Drug: bortezomib; Drug: dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Confirmed Disease Response
The primary efficacy analysis was based on the best response obtained during the treatment period according to the European Group for Blood and Marrow Transplantation (EBMT) criteria as assessed by the investigator. The best confirmed response was defined as 2 separate and consecutive evaluations of response, at least 6 weeks apart (for progressive disease [PD], 1 to 3 weeks apart). The ordering of the responses was: complete response (CR), partial response (PR), minimal response (MR), no change (NC) and PD. CR was the best response and the poorest response was PD.
Measured: every 28 days during treatment period for up to 6 to 8 cycles
Best Reported Disease Response
The primary efficacy analysis was based on the best response obtained during the treatment period according to the EBMT criteria as assessed by the investigator. The ordering of the responses was: CR, PR, MR, NC and PD. CR was the best response and the poorest response was PD.
Measured: every 28 days during treatment period for up to 6 to 8 cycles
Secondary outcomes (1)
Duration of Response (DOR)
DOR was defined as the duration from the date of the best confirmed response for subjects who achieved CR or PR to the date of first documented evidence of PD (or relapse for subjects who experienced CR) over the duration of the study. DOR = ([Date of PD or date of censoring - Date of best response]+1)/30.44.
Measured: every 28 days during treatment period for up to 6 to 8 cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2007 (estimated)
- Study startDec 2006
- Primary completionJan 2008
- Study completionJan 2008
Why it stopped: TRIAL STOPPED due to a change in standard of care and the required patient numbers could no longer be achieved
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.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen-Cilag International NV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen-Cilag International NV Clinical Trial, Study director, Janssen-Cilag International NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441168
- Sponsor's protocol ID
- CR011065
- Other IDs
- 26866138MMY2038, 2006-001709-27
- Status last verified
- Feb 2014
- First submitted
- 27 Feb 2007
- Last updated
- 21 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Velcade When Added to Adriamycin-Dexamethasone Treatment Versus Vincristine-Adriamycin-Dexamethasone Standard Treatment in Subjects With Multiple Myeloma Who Are Refractory to or Have Relapsed After Primary Therapy for Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00441168
- Acronym / sponsor ID
- CR011065
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, bortezomib, Cancer, Hematology, bone marrow, immunoglobulin, relapse, refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: TRIAL STOPPED due to a change in standard of care and the required patient numbers could no longer be achieved
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Janssen-Cilag International NVIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 28 Feb 2007 (estimated)
- Results
- Posted 21 Mar 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 research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in patients with multiple myeloma. Multiple Myeloma is the second most common cancer of the blood. Bortezomib is the first approved cancer treatment in a new class of medicines called proteasome inhibitors. It disrupts the cell cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells. The treatment will be used as second line treatment, which means either the disease has returned after a period of improvement (relapse) or the disease did not respond to the initial treatment (refractory). Patients will receive either bortezomib (PS341), doxorubicin (Adriamycin) and dexamethasone (PAD) or the VAD standard therapy.
Detailed description
Bortezomib, has been approved for use in patients with multiple myeloma, who have already received at least one prior treatment and whose disease is worsening on their last treatment and who have already undergone or are unsuitable for bone marrow transplantation. Bortezomib has significant activity in patients with relapsed multiple myeloma, its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin. The VAD combination has been widely used in multiple myeloma and has demonstrated to be effective in relapsed patients. Based on previous trial results, it is hoped that bortezomib, in replacing vincristine in the VAD standard therapy, can improve the response to treatment of patients with multiple myeloma, with manageable side effects. This is an international, multicentre, randomised, open-label, parallel group study. About 212 patients will take part in the study. Patients will be treated with either bortezomib (PS-341), Adriamycin and Dexamethasone (PAD) or Vincristine, Adriamycin and Dexamethasone (VAD). There will be an initial 14 day screening period to evaluate if the patient is suitable for the study. After screening, eligible patients will be randomised to receive either PAD or VAD. Patients will receive therapy for up to 8 treatment cycles of 28 days each. After the treatment period, there will be a long-term follow-up period with monthly visits until disease progression or relapse. Thereafter follow-up will be continued by at least a phone call every other month. This long-term follow-up period will be performed for all patients until the last patient was treated and followed up for 1 year. Response to treatment will be assessed according to the European group for blood and marrow transplant criteria (EBMT). Disease burden will be monitored by measuring M-protein concentration in serum and in urine every 4 weeks until disease progression or relapse. Thereafter follow-up for survival will be continued every other month by at least a phone call. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examination and clinical laboratory tests. Treatment with PAD or VAD will be for up to 8 cycles of 28 days each. Treatment beyond 6 cycles will be discussed on individual basis. Proposed dosages are: bortezomib 1.3 mg/m² intravenous (IV) bolus on Days 1, 4, 8, and 11; vincristine 0.4mg IV push on Days 1 to 4; doxorubicin 9mg/m² IV push on Days 1 to 4; dexamethasone in 1st cycle 40 mg daily on Days 1 to 4, 9 to 12 and 17 to 20, orally (or equivalent parenteral dose) and on subsequent cycles as 40 mg daily on Days 1 to 4 and 17 to 20 only.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VAD Treatment | Active comparator | Drug: adriamycin, Drug: dexamethasone, Drug: vincristinevincristine in combination with adriamycin and dexamethasone |
| PAD Treatment | Experimental | Drug: adriamycin, Drug: bortezomib, Drug: dexamethasonebortezomib in combination with adriamycin and dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Relapsed or refractory multiple myeloma following 1 previous line of therapy and, is scheduled by the investigator to be treated with vincristine, adriamycin and dexamethasone standard therapy
- measurable secretory multiple myeloma based on defined criteria
- Karnofsky performance status of >or = 60%
- fulfils defined laboratory requirements within 14 days before baseline
- if female, the patient is either postmenopausal or surgically sterilised or willing to use an acceptable method of birth control for defined period of time
Key exclusion criteria (5 listed)
- More than one previous line of therapy for multiple myeloma
- use of bortezomib in the previous line of therapy and/or received bortezomib in a previous trial
- known allergy or hypersensitivity to bortezomib, boron or mannitol
- peripheral neuropathy or neuropathic pain of grade 2 or higher
- myocardial infarction within 6 months of enrollment or had New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
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 |
|---|---|---|
| adriamycinadriamycin: 9mg/m² intravenous (IV) push on days 1 to 4 | Drug | PAD Treatment, VAD Treatment |
| bortezomibbortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11 | Drug | PAD Treatment |
| dexamethasonedexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle | Drug | PAD Treatment, VAD Treatment |
| vincristinevincristine: 0.4mg IV push on days 1 to 4 | Drug | VAD Treatment |
Primary outcome
Best Confirmed Disease Response
Time frame: every 28 days during treatment period for up to 6 to 8 cycles
The primary efficacy analysis was based on the best response obtained during the treatment period according to the European Group for Blood and Marrow Transplantation (EBMT) criteria as assessed by the investigator. The best confirmed response was defined as 2 separate and consecutive evaluations of response, at least 6 weeks apart (for progressive disease [PD], 1 to 3 weeks apart). The ordering of the responses was: complete response (CR), partial response (PR), minimal response (MR), no change (NC) and PD. CR was the best response and the poorest response was PD.
Best Reported Disease Response
Time frame: every 28 days during treatment period for up to 6 to 8 cycles
The primary efficacy analysis was based on the best response obtained during the treatment period according to the EBMT criteria as assessed by the investigator. The ordering of the responses was: CR, PR, MR, NC and PD. CR was the best response and the poorest response was PD.
1 secondary outcome
Duration of Response (DOR)
Time frame: every 28 days during treatment period for up to 6 to 8 cycles
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Janssen-Cilag International NV Clinical Trial study director
Janssen-Cilag International NV
16 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing adriamycin, bortezomib and dexamethasone in people with Multiple Myeloma, run by Janssen-Cilag International NV at 16 sites in 7 countries.
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 6 inclusion and 5 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: stopped early, as of the sponsor's last update on 21 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Lithuania, Poland, Russia, Turkey (Türkiye), Germany and 2 more countries. 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 21 Mar 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?
Best Confirmed Disease Response (time frame: every 28 days during treatment period for up to 6 to 8 cycles). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Mar 2014.