Multiple MyelomaPhase 2NCT01492881
Study of Vorinostat With Doxil and Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing Vorinostat, Bortezomib and pegylated liposomal doxorubicin in people with Multiple Myeloma, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this research study is to determine how multiple myeloma responds when the study drug vorinostat is added to the standard treatment of bortezomib and pegylated liposomal doxorubicin (PLD). 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?
- Vorinostat, Bortezomib and pegylated liposomal doxorubicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Jan 2017
- 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
- Relapsed or relapsed and refractory multiple myeloma:
- Relapsed MM is defined as clinically active disease, in patients who have received one or more prior therapies, that is not refractory to the most recent treatment. (Refractory to the prior treatment means either progressive disease (PD) on last prior therapy; best response of stable disease (SD) to last prior therapy, or PD within 60 days of completing therapy).
- Relapsed and refractory MM is defined as relapsed disease, which either becomes non-responsive while on salvage therapy, or progresses within 60 days of last therapy.
- 1 to 3 prior lines of therapy for multiple myeloma (a single line of treatment may consist of 1 or more agents and regimens. A single line of therapy may be most easily delineated by a response to treatment followed by a change in treatment due to the progression of disease.
- Prior bortezomib- and anthracycline-based therapy is allowed; prior cumulative doxorubicin dose must be <360 mg/m2 (or its equivalent)
- Prior autologous stem cell transplantation is allowed provided the patient is 3 months out from transplant and has recovered from any transplant-related toxicities (to baseline or grade 1 in severity)
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- All prior treatment-related non-hematologic toxicities resolved to ≤Grade 1 (or baseline), not including alopecia
- Prior radiation therapy completed ≥2 weeks prior to day 1 of treatment Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Age ≥18 years
- Life expectancy of at least 6 months
- Adequate bone marrow function (without platelet or RBC transfusion support within one week of screening) as demonstrated by:
- Hemoglobin ≥ 8 g/dL (use of erythropoietin stimulating agent is OK)
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (without granulocyte growth factor support)
- Platelet count ≥ 100,000/mm3 (≥75,000/mm3 in patients with ≥30% marrow involvement of MM who are felt to have thrombocytopenia primarily due to marrow infiltration of disease as opposed to diminished marrow reserves from prior therapy)
- Adequate hepatic and renal function as demonstrated by:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Total serum bilirubin ≤1.5 x ULN
- Creatinine clearance (CrCL) ≥ 30mL/min as measured via Cockcroft-Gault or 24-hour urine testing
- Documented negative serologic testing for hepatitis B (HBV) and Hepatitis C (HCV) as measured by the following (NOTE: this testing is not necessary if patient has had negative testing within the last year, and no subsequent risk factors for acquisition of these viruses):
- HBV surface antigen, surface antibody, and core antibody (NOTE: patients who are seropositive because of hepatitis B vaccine are eligible)
- HCV antibody.
- For patients with serologic evidence of viral hepatitis, quantitative PCR will be performed.
- Documented negative HIV blood test (NOTE: this testing is not necessary if patient has had negative testing within the last year, and no subsequent risk factors for acquisition of this virus)
- Adequate cardiac function, defined as:
- No EKG evidence of acute ischemia
- No EKG evidence of active clinically significant conduction system abnormalities
- No EKG evidence of > Grade 2 (>480 ms) QTc prolongation
- Prior to study entry, any ECG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant
- No uncontrolled angina or severe ventricular arrhythmias
- No clinically significant pericardial disease
- No history of myocardial infarction within the last 6 months
- Left ventricular ejection fraction (LVEF) must be > 45% by either echocardiography or radionuclide-based multiple gated acquisition (MUGA)
- No Class II or higher New York Heart Association Congestive Heart Failure
- Negative serum β-hCG pregnancy test within 72 hours of day 1 of treatment with study medications in women of child-bearing potential
- All males and females of childbearing potential must agree to use an effective contraceptive method during the study and for 3 months following the last dose of study treatment. Effective contraception is defined as any medically recommended method (or combination of methods) as per standard of care, including abstinence. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
Who cannot join
- > 3 prior lines of therapy for treatment of MM
- Receipt of prior allogeneic stem cell/bone marrow transplantation
- Primary refractory MM as defined by the ASH/FDA Workshop on Clinical Endpoints in Multiple Myeloma[24]
- Peripheral neuropathy (PN) ≥ grade 1 with pain or ≥grade 2 PN within 14 days prior to enrollment
- Known history of HIV, HBV or HCV infection
- Serum potassium ≤3.0 mmol/L or serum magnesium ≤1.6mg/dL that cannot be corrected with supplementation
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- Known hypersensitivity to bortezomib or any of its components (boron, mannitol), vorinostat, doxorubicin, or any of the components of PLD; Patients with a history of reactions to other liposomal drug formulations will be evaluated individually, and if their reactions were felt to have been due to the liposome itself, as opposed to the encapsulated agent, they will be excluded at the discretion of the investigators.
- Prior or concomitant use of a histone deacetylase inhibitor (exception: prior valproic acid for epilepsy is allowed provided patient undergoes a 30 day wash out prior to D1 of study treatment)
- No major surgery within 3 weeks prior to day 1 of study treatment
- Active, serious infection, medical, or psychiatric condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective
- Other prior or concomitant malignancies with the exception of:
- Non-melanoma skin cancer
- In-situ malignancy
- Low-risk prostate cancer after curative therapy
- Other cancer for which the patient has been disease free for ≥ 3 years
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comphrehensive Cancer Center at University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: A Multi-Center, Single-Arm, Phase II Study of Vorinostat (V) in Combination With Pegylated Liposomal Doxorubicin (PLD) and Bortezomib (B) Followed by VB Maintenance in Patients With Relapsed and Relapsed/Refractory Multiple Myeloma
The purpose of this research study is to determine how multiple myeloma responds when the study drug vorinostat is added to the standard treatment of bortezomib and pegylated liposomal doxorubicin (PLD). After participants complete the three drug combination and if their multiple myeloma has decreased, the investigators also want to learn what effects (both good and bad) when vorinostat and bortezomib are given to people with multiple myeloma over a longer period of time. This type of treatment is called 'Maintenance Therapy'.
Read the detailed description
This is a prospective, open-label single arm phase II trial of vorinostat, bortezomib and pegylated liposomal doxorubicin (PLD) followed by vorinostat/bortezomib (VB) maintenance therapy for patients with relapsed and relapsed and refractory multiple myeloma (MM). The primary hypothesis being evaluated is that the addition of vorinostat to the PLD and bortezomib backbone (VB-PLD) will improve the overall response rate (ORR) as compared to a historical control of PLD in combination with bortezomib.[1] We anticipate that the addition of maintenance therapy will not improve the ORR, but may improve the quality (depth) of response and progression free survival (PFS).
Secondary endpoints include PFS, high quality response rates (very good partial responses (VGPR) + complete responses (CRs)), duration of remission (DOR), quality of life (QOL), overall survival (OS) and tolerability of the regimen in patients with relapsed and relapsed and refractory multiple myeloma.
- Conditions
- Multiple Myeloma
- Being tested
- Vorinostat, Bortezomib, pegylated liposomal doxorubicin
- Keywords
- relapsed multiple myeloma, refractory multiple myeloma, vorinostat, bortezomib, doxil
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called Zolina
Oral, 400mg, taken days 4 through 11 of each cycle.
BortezomibDrug
Also called Velcade
subcutaneous injection, 1.3mg/m2, Days 1, 4, 8, and 11 every cycle
pegylated liposomal doxorubicinDrug
Also called Doxil
Intravenous, 30mg/m2, Day 4
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat, Bortezomib, Doxil | Experimental | Induction therapy will consist of up to 8 cycles of vorinostat, bortezomib, and doxil. One cycle is defined as 21 days.
Maintenance therapy will consist of Vorinostat and bortezomib. One maintenance cycle is 28 days and repeated for up to 1 year. Receives: Drug: Vorinostat; Drug: Bortezomib; Drug: pegylated liposomal doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the overall response rate.
Estimate the overall response rate (ORR) of the vorinostat, PLD and bortezomib regimen (VB/PLD) followed by vorinostat/bortezomib (VB) maintenance in patients with relapsed and relapsed/refractory multiple myeloma. Criteria for response will be based on the International Uniform Response Criteria for Multiple Myeloma, modified to incorporate criteria for minor response (MR). The overall response rate will be defined as the total number of patients whose response are PR or above, divided by the number of response evaluable patients.
Measured: 18 months
Secondary outcomes (4)
Evaluate the quality of life measures in patients.
QOL will be evaluated using the EORTC QLQ-C30 and QLQ-MY20 survey instruments.
Measured: 18 months
Assess the safety and tolerability.
Safety will be assessed via the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4 (CTCAE v4). The analysis of safety will be based on the frequency of adverse events and their severity for patients who received any study medicine.
Measured: 18 months
Estimate the overall survival.
A patient's survival time will be defined as the time from start of treatment to the date of his or her death.
Measured: 36 months
Estimate Progression-free survival
A patient's progression-free survival (PFS) will be defined as the time from start of treatment until the date he or she has documented progression or dies.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2011 (estimated)
- Study startApr 2012
- Primary completionJan 2015 (estimated)
- Study completionJan 2017 (estimated)
Why it stopped: Doxil is currently unavailable
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.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Peter M Voorhees, MD, Principal investigator, Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01492881
- Sponsor's protocol ID
- LCCC 1119
- Status last verified
- May 2012
- First submitted
- 12 Dec 2011
- Last updated
- 11 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Single-Arm, Phase II Study of Vorinostat (V) in Combination With Pegylated Liposomal Doxorubicin (PLD) and Bortezomib (B) Followed by VB Maintenance in Patients With Relapsed and Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01492881
- Acronym / sponsor ID
- LCCC 1119
- Conditions
- Multiple Myeloma
- Keywords
- relapsed multiple myeloma, refractory multiple myeloma, vorinostat, bortezomib, doxil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Doxil is currently unavailable
- Enrolment
- 0 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2012
- Primary completion
- Jan 2015 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 15 Dec 2011 (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 research study is to determine how multiple myeloma responds when the study drug vorinostat is added to the standard treatment of bortezomib and pegylated liposomal doxorubicin (PLD). After participants complete the three drug combination and if their multiple myeloma has decreased, the investigators also want to learn what effects (both good and bad) when vorinostat and bortezomib are given to people with multiple myeloma over a longer period of time. This type of treatment is called 'Maintenance Therapy'.
Detailed description
This is a prospective, open-label single arm phase II trial of vorinostat, bortezomib and pegylated liposomal doxorubicin (PLD) followed by vorinostat/bortezomib (VB) maintenance therapy for patients with relapsed and relapsed and refractory multiple myeloma (MM). The primary hypothesis being evaluated is that the addition of vorinostat to the PLD and bortezomib backbone (VB-PLD) will improve the overall response rate (ORR) as compared to a historical control of PLD in combination with bortezomib.[1] We anticipate that the addition of maintenance therapy will not improve the ORR, but may improve the quality (depth) of response and progression free survival (PFS).
Secondary endpoints include PFS, high quality response rates (very good partial responses (VGPR) + complete responses (CRs)), duration of remission (DOR), quality of life (QOL), overall survival (OS) and tolerability of the regimen in patients with relapsed and relapsed and refractory multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat, Bortezomib, Doxil | Experimental | Drug: Vorinostat, Drug: Bortezomib, Drug: pegylated liposomal doxorubicinInduction therapy will consist of up to 8 cycles of vorinostat, bortezomib, and doxil. One cycle is defined as 21 days. Maintenance therapy will consist of Vorinostat and bortezomib. One maintenance cycle is 28 days and repeated for up to 1 year. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Relapsed MM is defined as clinically active disease, in patients who have received one or more prior therapies, that is not refractory to the most recent treatment. (Refractory to the prior treatment means either progressive disease (PD) on last prior therapy; best response of stable disease (SD) to last prior therapy, or PD within 60 days of completing therapy).
- Relapsed and refractory MM is defined as relapsed disease, which either becomes non-responsive while on salvage therapy, or progresses within 60 days of last therapy.
- 1 to 3 prior lines of therapy for multiple myeloma (a single line of treatment may consist of 1 or more agents and regimens. A single line of therapy may be most easily delineated by a response to treatment followed by a change in treatment due to the progression of disease.
- Prior bortezomib- and anthracycline-based therapy is allowed; prior cumulative doxorubicin dose must be <360 mg/m2 (or its equivalent)
- Prior autologous stem cell transplantation is allowed provided the patient is 3 months out from transplant and has recovered from any transplant-related toxicities (to baseline or grade 1 in severity)
Key exclusion criteria (16 listed)
- > 3 prior lines of therapy for treatment of MM
- Receipt of prior allogeneic stem cell/bone marrow transplantation
- Primary refractory MM as defined by the ASH/FDA Workshop on Clinical Endpoints in Multiple Myeloma[24]
- Peripheral neuropathy (PN) ≥ grade 1 with pain or ≥grade 2 PN within 14 days prior to enrollment
- Known history of HIV, HBV or HCV infection
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 |
|---|---|---|
| VorinostatAlso: ZolinaOral, 400mg, taken days 4 through 11 of each cycle. | Drug | Vorinostat, Bortezomib, Doxil |
| BortezomibAlso: Velcadesubcutaneous injection, 1.3mg/m2, Days 1, 4, 8, and 11 every cycle | Drug | Vorinostat, Bortezomib, Doxil |
| pegylated liposomal doxorubicinAlso: DoxilIntravenous, 30mg/m2, Day 4 | Drug | Vorinostat, Bortezomib, Doxil |
Primary outcome
Estimate the overall response rate.
Time frame: 18 months
Estimate the overall response rate (ORR) of the vorinostat, PLD and bortezomib regimen (VB/PLD) followed by vorinostat/bortezomib (VB) maintenance in patients with relapsed and relapsed/refractory multiple myeloma. Criteria for response will be based on the International Uniform Response Criteria for Multiple Myeloma, modified to incorporate criteria for minor response (MR). The overall response rate will be defined as the total number of patients whose response are PR or above, divided by the number of response evaluable patients.
4 secondary outcomes
Evaluate the quality of life measures in patients.
Time frame: 18 months
Assess the safety and tolerability.
Time frame: 18 months
Estimate the overall survival.
Time frame: 36 months
Estimate Progression-free survival
Time frame: 36 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2012.
- UNC Lineberger Comprehensive Cancer Center N.C. Cancer HospitalLink provided by the sponsor.
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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.
Peter M Voorhees, MD principal investigator
Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill
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 Vorinostat, Bortezomib and pegylated liposomal doxorubicin in people with Multiple Myeloma, run by UNC Lineberger Comprehensive Cancer Center 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 35 inclusion and 16 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: withdrawn, as of the sponsor's last update on 11 May 2012. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Estimate the overall response rate. (time frame: 18 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 11 May 2012.