Multiple Myeloma and Plasma Cell NeoplasmPhase 2NCT00814541
PAD. ICORG 05-01, V11
A Phase 2 study testing Bortezomib, Doxorubicin and Dexamethasone in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Cancer Trials Ireland at 9 sites in 2 countries.
Trial summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- Bortezomib, Doxorubicin and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Dec 2005to Dec 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Patients aged at least 18 years with MM requiring therapy for relapsed or refractory disease.
- Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup allocation is shown in 4.1
- Measurable serum and/or urine paraprotein, or serum free light chain
- Performance Status (PS) 0-3 (ECOG - see Appendix B)
- Serum bilirubin values <1.5 times the upper limit of normal
- Serum ALT/AST values <2.5 times the upper limit of normal
- Able to give informed consent
Who cannot join
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Females of child-bearing potential without a negative pregnancy test, immediately prior to the start of PAD therapy and/or unwilling to use barrier contraceptive precautions throughout the study or who are pregnant or breast-feeding
- Men with partners of child bearing potential unwilling to use a medically acceptable form of contraception
- Patients with non-secretory MM and no measurable elevation of serum free light chain
- Performance status 4 (ECOG)
- Patient has a platelet count <75 x 10^9/L within 14 days before enrolment
Show all 18Show fewer
- Patient has an absolute neutrophil count <1.0 x 10^9/L within 14 days before enrolment
- Patient has a serum creatinine > 400 micromol/l at the time of enrolment
- Patient has Grade 2 or greater than Grade 2 peripheral neuropathy or neuropathic pain as defined by NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) within 14 days before enrolment
- Cardiac ejection fraction <40% by echocardiography or MUGA scan
- Known HIV seropositivity (obligatory testing is not necessary)
- Known Hepatitis B or C (obligatory testing is not necessary)
- Patients who have received more than one autologous transplant
- Use of any investigational drug within 4 weeks prior to enrolment or any patients scheduled to receive any investigational drug during the course of the study
- Previous Bortezomib therapy
- Patients who have a medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patient's participation in this study
- Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumours may be entered
- Plasma exchange within 21 days of enrolment
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Ireland5 sites
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Dublin, 24
Mater Misericordiae University Hospital
Dublin, 7
St. James's Hospital
Dublin, 8
University College Hospital
Galway
Mid-Western Cancer Centre at Mid-Western Regional Hospital
Limerick, 0009
United Kingdom4 sites
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
Belfast, Northern Ireland, BT9 7AB
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Saint Bartholomew's Hospital
London, England, EC1A 7BE
University College Hospital
London, England, NW1 2BU
About this study
Official title: Phase II Study to Assess the Safety, Efficacy, and Tolerability of Combination Therapy With Velcade (Bortezomib), Doxorubicin, and Dexamethasone (PAD) as Therapy for Patients With Relapsed or Refractory Multiple Myeloma
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin and dexamethasone works in treating patients with multiple myeloma that has relapsed or not responded to treatment.
PATIENT POPULATION: Patients with relapsed or refractory multiple myeloma requiring therapy will be invited to participate in this study. Eligible patients will be >18 years old and able to give fully informed consent. Patients must have a Performance Score (PS) of 0-3 (ECOG), measurable serum and/or urine paraprotein, or serum free light chain, bilirubin value of less than one and a half times the upper limit of normal with ALT/AST values less than two and a half times the upper limit of normal. Patients with non-secretory multiple myeloma are excluded from this study.
Read the detailed description
OBJECTIVES:
Primary
- To assess the response (partial and complete response) in patients with relapsed or refractory multiple myeloma receiving bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) after prior treatment with a maximum of 6 courses of vincristine, doxorubicin, and dexamethasone (VAD) or VAD-like regimen.
Secondary
- To assess the safety and toxicity of PAD therapy in these patients.
- To determine the progression-free survival and overall survival of these patients.
- To compare the original response to VAD with the response obtained with PAD as assessed by percent fall in paraprotein or Bence Jones Protein, lowest level of abnormal protein achieved, and duration of response in these patients.
OUTLINE: This is a multicenter study.
STUDY DESIGN \& METHODOLOGY:
This is a non-randomised, open labelled phase II trial in patients with relapsed or refractory multiple myeloma. Patients will be treated with: Bortezomib 1.3mg/m^2 bolus IV injection days 1, 4, 8 \& 11 + Dexamethasone 40mg po on days 1, 2, 3, 4 + Doxorubicin 9mg/m^2/day IV continuous infusion over days 1 - 4. In addition, for the first cycle only, Dexamethasone will also be given at 40mg po on days 8 - 11 and 15 - 18.
Each treatment regimen will continue for a minimum of four - and up to six - cycles of 21 days (maximum response and 1 cycle).
This study planned to recruit a total of 69 patients in up to 8 centres in Ireland and the UK.
Patients will be enrolled in three groups of 23 patients:
- Relapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and Z-Dex are examples of VAD like therapy) and who have had autologous transplants at least 1 year previously. Patients may proceed directly to PAD therapy or have had a maximum of one other line of therapy before PAD.
- Relapsed patients, previously treated with VAD or VAD-like regimen who have not had autologous transplantation and achieved at least PR (Appendix A). Patients may proceed directly to PAD therapy or have had a maximum of two other lines of therapy before PAD.
- Patients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR.
After completion of study treatment, patients are followed every 2 months for 1 year.
- Being tested
- Bortezomib, Doxorubicin, Dexamethasone
- Keywords
- refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
DoxorubicinDrug
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Relapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and Z-Dex are examples of VAD like therapy) and who have had autologous transplants at least 1 year previously.Patients may proceed directly to PAD therapy or have had a maximum of one other line of therapy before PAD. Receives: Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone |
| 2 | Experimental | Relapsed patients, previously treated with VAD or VAD-like regimen who have not had autologous transplantation and achieved at least PR (Appendix A). Patients may proceed directly to PAD therapy or have had a maximum of two other lines of therapy before PAD. Receives: Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone |
| 3 | Experimental | Patients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR. Receives: Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate (complete and partial response)
Measured: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Secondary outcomes (3)
Progression-free survival
Measured: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Overall survival
Measured: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Compare original response to vincristine, doxorubicin, and dexamethasone with response to bortezomib, doxorubicin hydrochloride, and dexamethasone
Measured: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2008 (estimated)
- Study startDec 2005
- Primary completionJun 2009
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Trials Ireland
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Curly Morris, Principal investigator, Belfast City Hospital Trust Incorporating Belvoir Park Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00814541
- Sponsor's protocol ID
- 05-01 ICORG
- Other IDs
- ICORG-05-01, 2005-000395-41, EU-20893, 2005
- Status last verified
- Jan 2014
- First submitted
- 24 Dec 2008
- Last updated
- 31 Dec 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Assess the Safety, Efficacy, and Tolerability of Combination Therapy With Velcade (Bortezomib), Doxorubicin, and Dexamethasone (PAD) as Therapy for Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00814541
- Acronym / sponsor ID
- 05-01 ICORG
- Keywords
- refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Cancer Trials IrelandResearch network
- Study start
- Dec 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 25 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin and dexamethasone works in treating patients with multiple myeloma that has relapsed or not responded to treatment.
PATIENT POPULATION: Patients with relapsed or refractory multiple myeloma requiring therapy will be invited to participate in this study. Eligible patients will be >18 years old and able to give fully informed consent. Patients must have a Performance Score (PS) of 0-3 (ECOG), measurable serum and/or urine paraprotein, or serum free light chain, bilirubin value of less than one and a half times the upper limit of normal with ALT/AST values less than two and a half times the upper limit of normal. Patients with non-secretory multiple myeloma are excluded from this study.
Detailed description
OBJECTIVES:
Primary
- To assess the response (partial and complete response) in patients with relapsed or refractory multiple myeloma receiving bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) after prior treatment with a maximum of 6 courses of vincristine, doxorubicin, and dexamethasone (VAD) or VAD-like regimen.
Secondary
- To assess the safety and toxicity of PAD therapy in these patients.
- To determine the progression-free survival and overall survival of these patients.
- To compare the original response to VAD with the response obtained with PAD as assessed by percent fall in paraprotein or Bence Jones Protein, lowest level of abnormal protein achieved, and duration of response in these patients.
OUTLINE: This is a multicenter study.
STUDY DESIGN \& METHODOLOGY:
This is a non-randomised, open labelled phase II trial in patients with relapsed or refractory multiple myeloma. Patients will be treated with: Bortezomib 1.3mg/m^2 bolus IV injection days 1, 4, 8 \& 11 + Dexamethasone 40mg po on days 1, 2, 3, 4 + Doxorubicin 9mg/m^2/day IV continuous infusion over days 1 - 4. In addition, for the first cycle only, Dexamethasone will also be given at 40mg po on days 8 - 11 and 15 - 18.
Each treatment regimen will continue for a minimum of four - and up to six - cycles of 21 days (maximum response and 1 cycle).
This study planned to recruit a total of 69 patients in up to 8 centres in Ireland and the UK.
Patients will be enrolled in three groups of 23 patients:
- Relapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and Z-Dex are examples of VAD like therapy) and who have had autologous transplants at least 1 year previously. Patients may proceed directly to PAD therapy or have had a maximum of one other line of therapy before PAD.
- Relapsed patients, previously treated with VAD or VAD-like regimen who have not had autologous transplantation and achieved at least PR (Appendix A). Patients may proceed directly to PAD therapy or have had a maximum of two other lines of therapy before PAD.
- Patients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR.
After completion of study treatment, patients are followed every 2 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Bortezomib, Drug: Doxorubicin, Drug: DexamethasoneRelapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and Z-Dex are examples of VAD like therapy) and who have had autologous transplants at least 1 year previously.Patients may proceed directly to PAD therapy or have had a maximum of one other line of therapy before PAD. |
| 2 | Experimental | Drug: Bortezomib, Drug: Doxorubicin, Drug: DexamethasoneRelapsed patients, previously treated with VAD or VAD-like regimen who have not had autologous transplantation and achieved at least PR (Appendix A). Patients may proceed directly to PAD therapy or have had a maximum of two other lines of therapy before PAD. |
| 3 | Experimental | Drug: Bortezomib, Drug: Doxorubicin, Drug: DexamethasonePatients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Patients aged at least 18 years with MM requiring therapy for relapsed or refractory disease.
- Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup allocation is shown in 4.1
- Measurable serum and/or urine paraprotein, or serum free light chain
- Performance Status (PS) 0-3 (ECOG - see Appendix B)
Key exclusion criteria (18 listed)
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Females of child-bearing potential without a negative pregnancy test, immediately prior to the start of PAD therapy and/or unwilling to use barrier contraceptive precautions throughout the study or who are pregnant or breast-feeding
- Men with partners of child bearing potential unwilling to use a medically acceptable form of contraception
- Patients with non-secretory MM and no measurable elevation of serum free light chain
- Performance status 4 (ECOG)
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 |
|---|---|---|
| Bortezomib | Drug | 1, 2, 3 |
| Doxorubicin | Drug | 1, 2, 3 |
| Dexamethasone | Drug | 1, 2, 3 |
Primary outcome
Response rate (complete and partial response)
Time frame: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
3 secondary outcomes
Progression-free survival
Time frame: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Overall survival
Time frame: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Compare original response to vincristine, doxorubicin, and dexamethasone with response to bortezomib, doxorubicin hydrochloride, and dexamethasone
Time frame: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2014.
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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.
Curly Morris principal investigator
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Doxorubicin and Dexamethasone in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Cancer Trials Ireland at 9 sites in 2 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 8 inclusion and 18 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 31 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Ireland, United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Response rate (complete and partial response) (time frame: Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.). 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 31 Dec 2014.