Multiple MyelomaPhase 2NCT01160484
Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide for Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing DVD-R in people with Multiple Myeloma, run by Oncotherapeutics at 8 sites in United States.
Trial summary
This is a phase II, multicenter, open label, nonrandomized study to evaluate the efficacy and safety of lenalidomide at a dose of 10 mg/dose in combination with bortezomib at 1.0 mg/m2/dose, pegylated liposomal doxorubicin (PLD) at 4.0 mg/m2/dose, and intravenous (IV) dexamethasone at 40 mg/dose in adult patients with… 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?
- DVD-R
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 8 sitesUnited States
- Study dates
- Sep 2009to Sep 2012
- 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 multiple myeloma (MM) based on standard criteria (Durie 1986)
- Currently has MM with measurable disease (serum m protein > 1.0g/dl and/or 24 hr urine m protein > 200mg/24 hr)
- Currently has progressive MM that has relapsed or is refractory
- Voluntarily signed an informed consent
- Age 18 years
- Eastern Cooperative Oncology Group (ECOG) performance < 2
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- Life-expectancy > 3 months
- Laboratory test results within these ranges:
- Absolute neutrophil count (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
- Hg > 8 g/dL
- Calculated or measured creatinine clearance > 30 mL/minute.
- Total bilirubin 2.0 x upper limit of normal (ULN)
- Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) 3 x ULN or 5 x ULN if hepatic metastases are present
- Serum potassium within the normal range
- Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
- Registered into the mandatory RevAssist® program, willing and able to comply with the requirements of RevAssist®.
- Females of childbearing potential must have a negative serum or urine pregnancy test and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin)
Who cannot join
- Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome
- Plasma cell leukemia
- Grade 2 peripheral neuropathy within 14 days before enrollment
- Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, Uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or Multigated acquisition(MUGA) scan evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
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- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (Kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a patient with a recent history of kyphoplasty with the medical monitor).
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)
- Received the following prior therapy:
- Chemotherapy within 3 weeks of enrollment (6 wks for nitrosoureas)
- Corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks of enrollment
- Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide or bortezomib within 21 days before enrollment
- Radiation therapy within 28 days before enrollment, except localized radiation therapy
- Use of any other experimental drug or therapy within 28 days of enrollment
- Known hypersensitivity to compounds of similar to thalidomide, doxorubicin, bortezomib, boron or mannitol.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
- Concurrent use of other anti-cancer agents or treatments
- Known positivity for human immunodeficiency virus (HIV) or hepatitis B or C; baseline testing for HIV and hepatitis B or C is not required
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Comprehensive Blood and Cancer Center
Bakersfield, California, 93309
Bassett Cancer Institute
Cooperstown, New York, 13326
Hematology-Oncology Medical Group of Fresno, Inc.
Fresno, California, 93720
Broome Oncology
Johnson City, New York, 13790
Watson Clinic, LLP, Center for Care and Research
Lakeland, Florida, 33805
Loma Linda University
Loma Linda, California, 92354
Santa Barbara Hematology Oncology
Santa Barbara, California, 93105
James R. Berenson, M.D., Inc.
West Hollywood, California, 90069
About this study
Official title: A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients With Relapsed/Refractory Multiple Myeloma
This is a phase II, multicenter, open label, nonrandomized study to evaluate the efficacy and safety of lenalidomide at a dose of 10 mg/dose in combination with bortezomib at 1.0 mg/m2/dose, pegylated liposomal doxorubicin (PLD) at 4.0 mg/m2/dose, and intravenous (IV) dexamethasone at 40 mg/dose in adult patients with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day 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
Studies have shown that combinations of PLD and bortezomib have striking synergy in preclinical studies and impressive response rates (73 \& 89%) in early clinical trials for MM patients with relapsed/refractory disease as well as first-line therapy. In addition, the efficacy of PLD with bortezomib in anthracycline-insensitive patients has been greater than single-agent bortezomib when comparing across studies. The immunomodulatory drugs, thalidomide and lenalidomide, target the tumor cell microenvironment, are antiangiogenic, have an immune activation effect and also exert a direct cytotoxic effect on myeloma cells. A phase 1 clinical study by our group also demonstrated that low dose PLD, administered at a more frequent dosing schedule, in combination with bortezomib, and dexamethasone (DVD regimen) is well tolerated and associated with high response rates and durable responses. In this phase II prospective trial, we will evaluate this regimen and show that this change enhances the DVD-R regimen's safety and efficacy for patients with relapsed/refractory MM.
- Conditions
- Multiple Myeloma
- Being tested
- DVD-R
- Keywords
- multiple myeloma, refractory, relapsed, bortezomib, doxil
- 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.
DVD-RDrug
Also called Decadron, Velcade, Doxil, Revlimid
40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
| Study group | Role | What they receive |
|---|---|---|
| DVD-R single arm | Experimental | Dose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin + Lenalidomide (DVD-R) Therapy:
Dexamethasone*- 40 mg IV Bortezomib- 1.0 mg/m2 IV Push Pegylated Liposomal Doxorubicin*- 4.0 mg/m2 IV Lenalidomide*- 10 mg PO
Per 28 Day Cycle
* Intravenous infusion (IV) Days 1, 4, 8 and 11 Intravenous push (IVP) Days 1, 4, 8 and 11 * Per Orem (PO) Days 1-14 Receives: Drug: DVD-R |
What is being measured
The primary outcome is the main question the study is designed to answer.
International Myeloma Working Group (IMWG) Response Criteria
The investigator will evaluate each patient for response to therapy according to criteria augmented from those developed by Bladé et al., 1998 presented below (Table 7-1). Assessment of disease response will be performed prior to drug administration on Day 1 of Cycles 2 8 and at the End of Study Treatment visit. If a patient is determined to have complete response (CR), very good partial response (VGPR), partial response (PR), or minor response (MR), then assessment of disease response is to be performed 4 weeks later to confirm the response.
Measured: Up to 7.5 months (eight 28-day cycles)
Secondary outcomes (6)
Time to First Response
Measured: Up to 7.5 months (eight 28-day cycles)
Time to Best Response
Measured: Up to 7.5 months (eight 28-day cycles)
Duration of Response
Measured: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.
Time to Progression
Measured: Time from the start of treatment to progressive disease
Progression-free Survival
Measured: Time from the start of treatment to progressive disease or until death
Follow-up Time
time that patients were monitored for disease progression and overall survival
Measured: Follow-up visits for disease progression and overall survival every 3 months after study discontinuation. After progression, follow-up visits for survival status every 6 months or until alternate therapy needs to be started or death intervenes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2010 (estimated)
- Study startSep 2009
- Primary completionDec 2011
- Study completionSep 2012
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.
- 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- James R. Berenson, MD, Principal investigator, James R. Berenson, MD, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01160484
- Sponsor's protocol ID
- RV-MM-PI-0533
- Status last verified
- Apr 2015
- First submitted
- 7 Jul 2010
- Last updated
- 4 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Berenson JR, Yellin O, Kazamel T, Hilger JD, Chen CS, Cartmell A, Woliver T, Flam M, Bravin E, Nassir Y, Vescio R, Swift RA. A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma. Leukemia. 2012 Jul;26(7):1675-80. doi: 10.1038/leu.2012.51. Epub 2012 Feb 22.
PubMed 22354206
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01160484
- Acronym / sponsor ID
- RV-MM-PI-0533
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, refractory, relapsed, bortezomib, doxil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- OncotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Celgene Corporation
- Study start
- Sep 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 12 Jul 2010 (estimated)
- Results
- Posted 21 Apr 2014
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 II, multicenter, open label, nonrandomized study to evaluate the efficacy and safety of lenalidomide at a dose of 10 mg/dose in combination with bortezomib at 1.0 mg/m2/dose, pegylated liposomal doxorubicin (PLD) at 4.0 mg/m2/dose, and intravenous (IV) dexamethasone at 40 mg/dose in adult patients with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day 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
Studies have shown that combinations of PLD and bortezomib have striking synergy in preclinical studies and impressive response rates (73 \& 89%) in early clinical trials for MM patients with relapsed/refractory disease as well as first-line therapy. In addition, the efficacy of PLD with bortezomib in anthracycline-insensitive patients has been greater than single-agent bortezomib when comparing across studies. The immunomodulatory drugs, thalidomide and lenalidomide, target the tumor cell microenvironment, are antiangiogenic, have an immune activation effect and also exert a direct cytotoxic effect on myeloma cells. A phase 1 clinical study by our group also demonstrated that low dose PLD, administered at a more frequent dosing schedule, in combination with bortezomib, and dexamethasone (DVD regimen) is well tolerated and associated with high response rates and durable responses. In this phase II prospective trial, we will evaluate this regimen and show that this change enhances the DVD-R regimen's safety and efficacy for patients with relapsed/refractory MM.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DVD-R single arm | Experimental | Drug: DVD-RDose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin + Lenalidomide (DVD-R) Therapy: Dexamethasone*- 40 mg IV Bortezomib- 1.0 mg/m2 IV Push Pegylated Liposomal Doxorubicin*- 4.0 mg/m2 IV Lenalidomide*- 10 mg PO Per 28 Day Cycle * Intravenous infusion (IV) Days 1, 4, 8 and 11 Intravenous push (IVP) Days 1, 4, 8 and 11 * Per Orem (PO) Days 1-14 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Has a diagnosis of multiple myeloma (MM) based on standard criteria (Durie 1986)
- Currently has MM with measurable disease (serum m protein > 1.0g/dl and/or 24 hr urine m protein > 200mg/24 hr)
- Currently has progressive MM that has relapsed or is refractory
- Voluntarily signed an informed consent
- Age 18 years
Key exclusion criteria (19 listed)
- Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome
- Plasma cell leukemia
- Grade 2 peripheral neuropathy within 14 days before enrollment
- Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, Uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or Multigated acquisition(MUGA) scan evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin
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 |
|---|---|---|
| DVD-RAlso: Decadron, Velcade, Doxil, Revlimid40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration. | Drug | DVD-R single arm |
Primary outcome
International Myeloma Working Group (IMWG) Response Criteria
Time frame: Up to 7.5 months (eight 28-day cycles)
The investigator will evaluate each patient for response to therapy according to criteria augmented from those developed by Bladé et al., 1998 presented below (Table 7-1). Assessment of disease response will be performed prior to drug administration on Day 1 of Cycles 2 8 and at the End of Study Treatment visit. If a patient is determined to have complete response (CR), very good partial response (VGPR), partial response (PR), or minor response (MR), then assessment of disease response is to be performed 4 weeks later to confirm the response.
6 secondary outcomes
Time to First Response
Time frame: Up to 7.5 months (eight 28-day cycles)
Time to Best Response
Time frame: Up to 7.5 months (eight 28-day cycles)
Duration of Response
Time frame: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.
Time to Progression
Time frame: Time from the start of treatment to progressive disease
Progression-free Survival
Time frame: Time from the start of treatment to progressive disease or until death
Follow-up Time
Time frame: Follow-up visits for disease progression and overall survival every 3 months after study discontinuation. After progression, follow-up visits for survival status every 6 months or until alternate therapy needs to be started or death intervenes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22354206Berenson JR, Yellin O, Kazamel T, Hilger JD, Chen CS, Cartmell A, Woliver T, Flam M, Bravin E, Nassir Y, Vescio R, Swift RA. A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma. Leukemia. 2012 Jul;26(7):1675-80. doi: 10.1038/leu.2012.51. Epub 2012 Feb 22.
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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, MD, Inc.
8 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 DVD-R in people with Multiple Myeloma, run by Oncotherapeutics at 8 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 19 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 4 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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 21 Apr 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?
International Myeloma Working Group (IMWG) Response Criteria (time frame: Up to 7.5 months (eight 28-day cycles)). 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 NCT01160484, 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 4 May 2015; AzTrials last refreshed its copy on 8 Nov 2026.