Multiple MyelomaPhase 2NCT01695330
Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens
A Phase 2 study testing Subcutaneous bortezomib in people with Multiple Myeloma, run by Oncotherapeutics at 1 site in United States.
Trial summary
This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will receive treatment with a SC bortezomib-containing combination regimen that does not contain thalidomide or vincristine. 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?
- Subcutaneous bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Oct 2015
- 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
- Has a diagnosis of MM based on the following:
- Major crit.:
- plasmacytomas on tissue biopsy
- bone marrow plasmacytosis (> 30% plasma cells)
- m-spike on serum electrophoresis IgG > 3.5 g/dL or IgA > 2.0 g/dL; kappa or lambda light chain excretion > 1 g/day on 24 hour urine protein electrophoresis
- Minor crit.:
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- bone marrow plasmacytosis (10% to 30% plasma cells)
- monoclonal Ig present but of lesser magnitude than given under major crit.
- lytic bone lesions
- normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
- Any of the following sets of crit. will confirm the diagnosis of MM:
- any 2 of the major crit.
- major criterion 1 plus minor criterion 2, 3, or 4
- major criterion 3 plus minor criterion 1 or 3
- minor crit. 1, 2, and 3, or 1, 2, and 4
- MM with measurable disease, defined as:
- a m-spike on serum electrophoresis of at least 0.5 g/dL and/or
- urine monoclonal protein levels of at least 200 mg/24 hours
- for patients without measurable serum and urine M-protein levels, an abnormal free light chain ratio (normal value: 0.26 - 1.65)
- Currently has progressive MM:
- Relapsed following stabilization or a response to at least one IV bortezomib (bort.) containing combination regimen that did not contain thalidomide or vincristine or refractory defined as progressed while receiving that anti-myeloma tx
- In between the IV bort.-based combination regimen and this study, the pt may have received other non-bort.-based regimens as long as these treatments did not contain thalidomide or vincristine
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
- Age: ≥18 yrs at the time of consent
- Able to adhere to the study visit schedule and other protocol requirements
- ECOG performance status of ≤ 2 at study entry
- Life-expectancy > 3 mos
- Laboratory test results w/in these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1, Day 1:
- ANC ≥ 1.5 x 109/L; if the bone marrow is extensively infiltrated (> 70% plasma cells) then ≥ 1.0 x 109/L
- Platelet count ≥ 75 x 109/L; if the bone marrow is extensively infiltrated (> 70% plasma cells) then ≥ 50 x 109/L
- Hgb > 8 g/dL
- Calculated or measured CrCl of at least 30 mL/min. (see protocol)
- Total Bili ≥ 1.5 x ULN
- AST (SGOT) and ALT (SGPT) ≥ 3 x ULN ≥ 5 x ULN if hepatic metastases are present
- Serum potassium WNL
- Female pt is either postmenopausal for 1 year or greater before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of VELCADE, or agree to completely abstain from heterosexual intercourse.
- Male patients who agree to 1) practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or 2) completely abstain from heterosexual intercourse.
Who cannot join
- POEMS syndrome
- PCL
- Primary amyloidosis
- Diagnosed or treated for another malignancy w/in 3 yrs of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- ≤ Grade 2 peripheral neuropathy
- Pt had myocardial infarction w/in 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.
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- Severe hypercalcemia, i.e., serum calcium ≤ 12 mg/dL (3.0 mmol/L) corrected for albumin
- Undergone major surgery w/in 28 days prior enrollment or has not recovered from side effects of such therapy (see protocol)
- Received the following prior therapy:
- Thalidomide or vincristine alone or as part of a treatment regimen administered between the last IV bort.-based regimen and Cycle 1, Day 1 on this study. However, prior exposure to thalidomide or vincristine is allowed.
- Chemotherapy w/in 21 days of study drugs (6 weeks for nitrosoureas)
- Corticosteroids (>10 mg/day prednisone or equivalent) w/in 21 days of study drugs unless steroids are being administered at that dose or greater as part of the new regimen
- Immunotherapy or antibody therapy as well as lenalidomide, arsenic trioxide or bort. w/in 21 days before study drugs
- Radiation therapy w/in 21 days before study drugs. (see protocol for exceptions)
- Use of any other experimental drug or therapy w/in 28 days of study drugs
- Participation in clinical trials with other investigational agents not included in this trial, w/in 14 days of the start of this trial and throughout the duration of this trial.
- Hypersensitivity to VELCADE (bort.), boron, or mannitol.
- Concurrent use of other anti-cancer agents or treatments
- Pregnant or lactating patients
- Serious medical or psychiatric illness
- Known positivity for HIV or hepatitis B or C
Trial locations and contacts
1 site in 1 country.
United States1 site
James R. berenson, M.D., Inc.
West Hollywood, California, 90069
About this study
Official title: A Phase II Study of Subcutaneous (SC) Bortezomib-Regimens for Patients With Relapsed/Refractory Multiple Myeloma (MM) Failing Prior Intravenous (IV) Bortezomib-Containing Regimens
This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will receive treatment with a SC bortezomib-containing combination regimen that does not contain thalidomide or vincristine. The patients will be required to have received a prior IV bortezomib containing combination regimen that did not contain thalidomide or vincristine and that differs from the SC bortezomib-containing one. In between the time that the patient received the IV bortezomib-based combination regimen and enrollment onto this study, patients may have received other non-bortezomib-based regimens as long as these treatments did not contain thalidomide or vincristine. This study will enroll patients who have relapsed or have become refractory to their prior IV-administered bortezomib-containing combination regimen as demonstrated by progressive disease while on or following that regimen. Patients must have received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4 weeks per cycle. Patients must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible. Patients who have relapsed or have become refractory to their most recent IV bortezomib-containing combination regimen are eligible regardless of when they received that regimen, as long as they meet the above criteria.
The study will consist of a screening period, followed by up to eight open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a follow-up period.
Read the detailed description
Primary Objectives:
- To establish the safety and tolerability of treatment with a SC bortezomib containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen:
- To compare the incidence of PN between IV bortezomib and treatment with SC bortezomib in a subsequent anti-MM combination regimen
- To compare the severity of PN between IV bortezomib and treatment with SC bortezomib in a subsequent combination anti-MM regimen
Secondary Objectives:
- To compare the overall response rate [combined CR + very good partial response (VGPR) + PR + MR] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen
- To compare disease parameters following treatment with a SC bortezomib containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen as follows:
- time to progression
- progression free survival
- time to first response
- duration of response
- overall survival
- To determine the incidence and severity of injection-site reactions with SC administration of bortezomib
- Conditions
- Multiple Myeloma
- Being tested
- Subcutaneous bortezomib
- Keywords
- Multiple Myeloma, Relapsed, Refractory, Bortezomib, Subcutaneous, Oncotherapeutics
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Subcutaneous bortezomibDrug
Also called Velcade
Bortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator.
| Study group | Role | What they receive |
|---|---|---|
| Subcutaneous bortezomib | Experimental | Not described Receives: Drug: Subcutaneous bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.
Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.
Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria.
Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.
Measured: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.
Secondary outcomes (1)
Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, & Determine Incidence and Severity of Injection-site Reactions.
Compare overall response rate [combined CR + very good partial response (VGPR) + PR + MR] and disease parameters [time to progression, -progression free survival, -time to first response, -duration of response, -overall survival] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease form a prior or different IV bortezomib-containing combination regimen. Determine incidence and severity of injection-site reactions with CS administration of bortezomib by number of patients with injection site reaction specific adverse events.
Measured: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2012 (estimated)
- Study startMay 2012
- Primary completionOct 2015
- Study completionOct 2015
Why it stopped: Terminated by Sponsor of this study.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- James R Berenson, MD, Principal investigator, James R. Berenson, M.D., Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01695330
- Sponsor's protocol ID
- X05384
- Status last verified
- Nov 2016
- First submitted
- 24 Aug 2012
- Last updated
- 16 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Subcutaneous (SC) Bortezomib-Regimens for Patients With Relapsed/Refractory Multiple Myeloma (MM) Failing Prior Intravenous (IV) Bortezomib-Containing Regimens
- ClinicalTrials.gov ID
- NCT01695330
- Acronym / sponsor ID
- X05384
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Relapsed, Refractory, Bortezomib, Subcutaneous, Oncotherapeutics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated by Sponsor of this study.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- OncotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- May 2012
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 27 Sep 2012 (estimated)
- Results
- Posted 16 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will receive treatment with a SC bortezomib-containing combination regimen that does not contain thalidomide or vincristine. The patients will be required to have received a prior IV bortezomib containing combination regimen that did not contain thalidomide or vincristine and that differs from the SC bortezomib-containing one. In between the time that the patient received the IV bortezomib-based combination regimen and enrollment onto this study, patients may have received other non-bortezomib-based regimens as long as these treatments did not contain thalidomide or vincristine. This study will enroll patients who have relapsed or have become refractory to their prior IV-administered bortezomib-containing combination regimen as demonstrated by progressive disease while on or following that regimen. Patients must have received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4 weeks per cycle. Patients must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible. Patients who have relapsed or have become refractory to their most recent IV bortezomib-containing combination regimen are eligible regardless of when they received that regimen, as long as they meet the above criteria.
The study will consist of a screening period, followed by up to eight open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a follow-up period.
Detailed description
Primary Objectives:
- To establish the safety and tolerability of treatment with a SC bortezomib containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen:
- To compare the incidence of PN between IV bortezomib and treatment with SC bortezomib in a subsequent anti-MM combination regimen
- To compare the severity of PN between IV bortezomib and treatment with SC bortezomib in a subsequent combination anti-MM regimen
Secondary Objectives:
- To compare the overall response rate [combined CR + very good partial response (VGPR) + PR + MR] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen
- To compare disease parameters following treatment with a SC bortezomib containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen as follows:
- time to progression
- progression free survival
- time to first response
- duration of response
- overall survival
- To determine the incidence and severity of injection-site reactions with SC administration of bortezomib
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subcutaneous bortezomib | Experimental | Drug: Subcutaneous bortezomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Has a diagnosis of MM based on the following:
- MM with measurable disease, defined as:
- Currently has progressive MM:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
- Age: ≥18 yrs at the time of consent
Key exclusion criteria (21 listed)
- POEMS syndrome
- PCL
- Primary amyloidosis
- Diagnosed or treated for another malignancy w/in 3 yrs of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- ≤ Grade 2 peripheral neuropathy
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 |
|---|---|---|
| Subcutaneous bortezomibAlso: VelcadeBortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator. | Drug | Subcutaneous bortezomib |
Primary outcome
The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.
Time frame: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.
Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit. Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria. Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.
1 secondary outcome
Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, & Determine Incidence and Severity of Injection-site Reactions.
Time frame: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2017.
- 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.
James R Berenson, MD principal investigator
James R. Berenson, M.D., Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Subcutaneous bortezomib in people with Multiple Myeloma, run by Oncotherapeutics at 1 site 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 37 inclusion and 21 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 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 16 Jan 2017). 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 Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen. (time frame: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.). 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 16 Jan 2017.