Multiple MyelomaPhase 1/2NCT01541332
Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma
A Phase 1/2 study testing Pomalidomide, Pegylated Liposomal Doxorubicin (PLD) and Dexamethasone in people with Multiple Myeloma, run by Oncotherapeutics at 8 sites in United States.
Trial summary
The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of a combination of three different drugs, pomalidomide, pegylated liposomal doxorubicin, and dexamethasone when used to treat relapsed (the disease came back) or refractory (the disease did not respond to… 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?
- Pomalidomide, Pegylated Liposomal Doxorubicin (PLD) and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 8 sitesUnited States
- Study dates
- Feb 2012to Dec 2016
- Phase
- Phase 1/2
- 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
- Diagnosis of MM based on standard criteria (Durie 1986)
- Currently has MM with measurable disease, defined as:
- a monoclonal immunoglobulin 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 that has relapsed or is refractory, defined as:
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- For the phase 1: Relapsed following stabilization or a response to at least one anti-myeloma regimen or refractory defined as progressed while receiving an anti-myeloma treatment
- For the phase 2: Refractory to lenalidomide as demonstrated by progressive disease while on lenalidomide or that relapsed within 8 weeks of the last dose of lenalidomide either as a single agent or in combination.
- Prior treatment with four days or less of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for MM will not be considered a regimen
- Able to adhere to the study visit schedule and other protocol requirements
- ECOG performance status of 2 or greater at study entry
- Life-expectancy of greater than 3 months
- Lab tests within study ranges at study entry:
- Absolute neutrophil count > 1.5 x 109/L
- Platelet count > 75 x 109/L
- Hemoglobin > 8 g/dL
- Calculated or measured creatinine clearance > 30 mL/minute
- Total bilirubin < 1.5 x upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) < 2 x ULN
- Serum potassium within the normal range
- Females of childbearing potential must have a negative serum or urine pregnancy test.
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to ASA may use warfarin or low molecular weight heparin)
Who cannot join
- POEMS syndrome
- Plasma cell leukemia
- Primary amyloidosis
- Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
- Impaired cardiac function or clinically significant cardiac diseases
- Severe hypercalcemia
Show all 21Show fewer
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF
- 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 subject 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:
- Pomalidomide
- Chemotherapy within 3 weeks of study drugs (6 wks for nitrosoureas)
- Corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks of study drugs
- Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide or bortezomib within 21 days before study drugs
- Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
- Use of any other experimental drug or therapy within 28 days of study drugs
- Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide, lenalidomide or doxorubicin.
- 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
Roy and Patricia Disney Family Cancer Center
Burbank, California, 91505
California Cancer Associates for Research and Excellence
Encinitas, California, 92024
Hematology Oncology Medical Group
Fresno, California, 93720
Illinois Cancer Specialists
Niles, Illinois, 60714
Pacific Cancer Care
Salinas, California, 93901
Cancer Center of Santa Barbara
Santa Barbara, California, 93105
Mission Hope Cancer Center
Santa Maria, California, 93454
James R Berenson, MD, Inc.
West Hollywood, California, 90069
About this study
Official title: A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma
The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of a combination of three different drugs, pomalidomide, pegylated liposomal doxorubicin, and dexamethasone when used to treat relapsed (the disease came back) or refractory (the disease did not respond to past treatment) multiple myeloma. Different dosages (amount of study drug) of pomalidomide are first being tested to determine if there are any side effects or risks associated with combining this study drug with the other two listed. Once the optimal dose is decided on, the study will change its focus to determining the effectiveness of the study drug in this combination.
Read the detailed description
This is a phase 1/2, multicenter, open label and nonrandomized study to evaluate the efficacy and safety of pomalidomide at daily dosages of 2, 3 or 4 mg in combination with intravenous (IV) dexamethasone at 40 mg/dose and Pegylated Liposomal Doxorubicin (PLD) at 5 mg/m2/dose for subjects 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, and a follow-up period.
Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles. Subjects are to be treated to a maximum response plus 2 additional cycles (no more than 8 cycles will be allowed) or complete 8 cycles of therapy without disease progression.
Pomalidomide, dexamethasone and PLD will be administered on the appropriate cycle days as shown below.
Cohort 1 Pomalidomide* - 2 mg, Dexamethasone - 40 mg, PLD - 5 mg/m2
Cohort 2 Pomalidomide* - 3 mg, Dexamethasone - 40 mg, PLD - 5 mg/m2
Cohort 3 Pomalidomide* - 4 mg, Dexamethasone - 40 mg, PLD - 5 mg/m2
- PO Days 1-21
** IV Days 1, 4, 8 and 11
In all cohorts, if an unacceptable dose limiting toxicities (DLT) is not seen in any of the 3 subjects during the first cycle of any dose level, dose escalation will continue. All subjects in a cohort must complete a minimum of 28 days or a full cycle, whichever is longer, without a DLT before enrollment to the next cohort can begin. If a DLT is identified in 1 subject at any dose level during the first treatment cycle, an additional 3 subjects will be recruited to this dose level. A maximum of 6 subjects may be enrolled in each cohort. If an unacceptable DLT is observed in 2 subjects at any dose level, no further subjects will be recruited to this dose level. The maximum tolerated dose (MTD) will be declared as the highest dose level at which fewer than 33% of subjects experienced an unacceptable DLT. If pomalidomide at 4 mg is reached and fewer than 33% of subjects experience an unacceptable DLT, 4 mg will be accepted as the putative MTD. Once the MTD is established, further enrollment will continue to expand that dose cohort until the total sample size of 40 subjects is reached for the entire study. During the phase 2 portion of this study, subjects enrolled will have relapsed/refractory MM resistant to lenalidomide as demonstrated by progressive disease while on lenalidomide or that has relapsed within 8 weeks of the last dose of lenalidomide.
- Conditions
- Multiple Myeloma
- Being tested
- Pomalidomide, Pegylated Liposomal Doxorubicin (PLD), Dexamethasone
- Keywords
- relapsed refractory, multiple myeloma, pomalidomide, Doxil, dexamethasone, Oncotherapeutics
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PomalidomideDrug
Also called CC-4047
Pomalidomide administered to 3 cohorts of subjects at escalating doses of 2 (cohort 1), 3 (cohort 2) and 4 mg/dose (cohort 3) per orem (PO). Doses are to be administered once-a-day, for the first 21 days, as part of a 28-day treatment cycle, followed by a 7-day rest period.
Pegylated Liposomal Doxorubicin (PLD)Drug
Also called Doxil
Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.
PLD will be given at a dose of 5.0 mg/m2 as a 60 minute IV 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.
DexamethasoneDrug
Also called Decadron
Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Pomalidomide + PLD + Dexamethasone | Experimental | Pomalidomide + Pegylated Liposomal Doxorubicin + Dexamethasone in an open label, dose escalation study Receives: Drug: Pomalidomide; Drug: Pegylated Liposomal Doxorubicin (PLD); Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of Pomalidomide
Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin
Measured: 12 months
Overall Response Rate
Phase 2: To determine efficacy as evidenced by the best overall response rate (CR + VGPR + PR + MR) following treatment with pomalidomide, dexamethasone and pegylated liposomal doxorubicin
Measured: 24 months
Secondary outcomes (6)
Number of Patients with Adverse Events
Phase 2: To establish the number of patients with adverse events when using the combination of pomalidomide, dexamethasone and pegylated liposomal doxorubicin
Measured: 24 months
Time to Progression
Phase 2: Defined as the time from initiation of therapy to progressive disease
Measured: 24 Months
Progression-free Survival
Phase 2: Defined as the time from initiation of therapy to progressive disease or death from any cause, which ever occurs first
Measured: 24 Months
Time to First Response
Phase 2: Defined as the time from the initiation of therapy to the first evidence of a confirmed response (CR, VGPR, PR or MR)
Measured: 24 Months
Duration of Response
Phase 2: Defined as the time from first response to progressive disease
Measured: 24 Months
Overall Survival
Phase 2: Defined as the time from initiation of therapy to death from any cause or last follow-up visit
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 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, Oncotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01541332
- Sponsor's protocol ID
- PO-MM-PI-0049
- Other IDs
- PDD-2011
- Status last verified
- Mar 2016
- First submitted
- 20 Feb 2012
- Last updated
- 10 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01541332
- Acronym / sponsor ID
- PO-MM-PI-0049
- Conditions
- Multiple Myeloma
- Keywords
- relapsed refractory, multiple myeloma, pomalidomide, Doxil, dexamethasone, Oncotherapeutics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (actual)
- Lead sponsor
- OncotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Celgene Corporation
- Study start
- Feb 2012
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 29 Feb 2012 (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.
The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of a combination of three different drugs, pomalidomide, pegylated liposomal doxorubicin, and dexamethasone when used to treat relapsed (the disease came back) or refractory (the disease did not respond to past treatment) multiple myeloma. Different dosages (amount of study drug) of pomalidomide are first being tested to determine if there are any side effects or risks associated with combining this study drug with the other two listed. Once the optimal dose is decided on, the study will change its focus to determining the effectiveness of the study drug in this combination.
Detailed description
This is a phase 1/2, multicenter, open label and nonrandomized study to evaluate the efficacy and safety of pomalidomide at daily dosages of 2, 3 or 4 mg in combination with intravenous (IV) dexamethasone at 40 mg/dose and Pegylated Liposomal Doxorubicin (PLD) at 5 mg/m2/dose for subjects 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, and a follow-up period.
Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles. Subjects are to be treated to a maximum response plus 2 additional cycles (no more than 8 cycles will be allowed) or complete 8 cycles of therapy without disease progression.
Pomalidomide, dexamethasone and PLD will be administered on the appropriate cycle days as shown below.
Cohort 1 Pomalidomide* - 2 mg, Dexamethasone - 40 mg, PLD - 5 mg/m2
Cohort 2 Pomalidomide* - 3 mg, Dexamethasone - 40 mg, PLD - 5 mg/m2
Cohort 3 Pomalidomide* - 4 mg, Dexamethasone - 40 mg, PLD - 5 mg/m2
- PO Days 1-21
** IV Days 1, 4, 8 and 11
In all cohorts, if an unacceptable dose limiting toxicities (DLT) is not seen in any of the 3 subjects during the first cycle of any dose level, dose escalation will continue. All subjects in a cohort must complete a minimum of 28 days or a full cycle, whichever is longer, without a DLT before enrollment to the next cohort can begin. If a DLT is identified in 1 subject at any dose level during the first treatment cycle, an additional 3 subjects will be recruited to this dose level. A maximum of 6 subjects may be enrolled in each cohort. If an unacceptable DLT is observed in 2 subjects at any dose level, no further subjects will be recruited to this dose level. The maximum tolerated dose (MTD) will be declared as the highest dose level at which fewer than 33% of subjects experienced an unacceptable DLT. If pomalidomide at 4 mg is reached and fewer than 33% of subjects experience an unacceptable DLT, 4 mg will be accepted as the putative MTD. Once the MTD is established, further enrollment will continue to expand that dose cohort until the total sample size of 40 subjects is reached for the entire study. During the phase 2 portion of this study, subjects enrolled will have relapsed/refractory MM resistant to lenalidomide as demonstrated by progressive disease while on lenalidomide or that has relapsed within 8 weeks of the last dose of lenalidomide.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pomalidomide + PLD + Dexamethasone | Experimental | Drug: Pomalidomide, Drug: Pegylated Liposomal Doxorubicin (PLD), Drug: DexamethasonePomalidomide + Pegylated Liposomal Doxorubicin + Dexamethasone in an open label, dose escalation study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Diagnosis of MM based on standard criteria (Durie 1986)
- Currently has MM with measurable disease, defined as:
- Currently has progressive MM that has relapsed or is refractory, defined as:
- Able to adhere to the study visit schedule and other protocol requirements
- ECOG performance status of 2 or greater at study entry
Key exclusion criteria (21 listed)
- POEMS syndrome
- Plasma cell leukemia
- Primary amyloidosis
- Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
- Impaired cardiac function or clinically significant cardiac diseases
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 |
|---|---|---|
| PomalidomideAlso: CC-4047Pomalidomide administered to 3 cohorts of subjects at escalating doses of 2 (cohort 1), 3 (cohort 2) and 4 mg/dose (cohort 3) per orem (PO). Doses are to be administered once-a-day, for the first 21 days, as part of a 28-day treatment cycle, followed by a 7-day rest period. | Drug | Pomalidomide + PLD + Dexamethasone |
| Pegylated Liposomal Doxorubicin (PLD)Also: DoxilDexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle. PLD will be given at a dose of 5.0 mg/m2 as a 60 minute IV 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. | Drug | Pomalidomide + PLD + Dexamethasone |
| DexamethasoneAlso: DecadronDexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle. | Drug | Pomalidomide + PLD + Dexamethasone |
Primary outcome
MTD of Pomalidomide
Time frame: 12 months
Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin
Overall Response Rate
Time frame: 24 months
Phase 2: To determine efficacy as evidenced by the best overall response rate (CR + VGPR + PR + MR) following treatment with pomalidomide, dexamethasone and pegylated liposomal doxorubicin
6 secondary outcomes
Number of Patients with Adverse Events
Time frame: 24 months
Time to Progression
Time frame: 24 Months
Progression-free Survival
Time frame: 24 Months
Time to First Response
Time frame: 24 Months
Duration of Response
Time frame: 24 Months
Overall Survival
Time frame: 24 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
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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
Oncotherapeutics
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pomalidomide, Pegylated Liposomal Doxorubicin (PLD) and Dexamethasone 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 22 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: status not confirmed, as of the sponsor's last update on 10 Mar 2016. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
MTD of Pomalidomide (time frame: 12 months). 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 10 Mar 2016.