Multiple MyelomaPhase 1NCT01038388
A Study of the Combination Vorinostat With Lenalidomide, Bortezomib and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma
A Phase 1 study testing Bortezomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Emory University at 1 site in United States.
Trial summary
The purpose of the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination. 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?
- Bortezomib, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2010to 5 Aug 2021
- Phase
- Phase 1
- 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
- Multiple Myeloma Diagnosis: Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria (ALL 3 REQUIRED):
- Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma.
- Monoclonal protein present in the serum and/or urine.
- Myeloma-related organ dysfunction (1 or more).
- [C] Calcium elevation in the blood S. Calcium >10.5 mg/l or upper limit of normal{}.
- [R] Renal insufficiency S. Creatinine > 2 mg/dl{}.
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- [A] Anemia Hemoglobin < 10 g/dl or 2 g < normal{}.
- [B] Lytic bone lesions or osteoporosis.
- Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma.
- Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period).
- Bisphosphonates are permitted
- Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. One week must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and one week have passed since the last date of therapy.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international unit (mIU)/mL 10 - 14 days prior to therapy and repeated again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- Age ≥ 18 years at the time of signing Informed Consent.
- All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment.
- Subject has a Karnofsky performance status of ≥ 60.
- Subject must be able to adhere to the study visit schedule and other protocol requirements.
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- 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
- Patient has ≥ Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
- Renal insufficiency (serum creatinine levels > 2.5 mg/dL).
- Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/mm³).
- Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm³. Growth factors may not be used to meet ANC eligibility criteria.
- Subjects with a hemoglobin < 8.0 g/dL.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN).
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- Concomitant therapy medications that include corticosteroids (except as indicated in inclusion criteria).
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic 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.
- Clinically relevant active infection requiring intravenous antibiotics.
- Serious co-morbid medical conditions such as chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
- Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
- Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or if the expected survival from other malignancy is greater than 90% at 5 years.
- Female subject is pregnant or breast-feeding.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment).
- Hypersensitivity to acyclovir or similar anti-viral drug.
- Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).
- Known HIV infection .
- Known active hepatitis B or C viral infection.
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: A Phase I Trial Evaluating the Safety and Efficacy of Vorinostat (Zolinza ®) + RVD (Lenalidomide {Revlimid ®} + Bortezomib {Velcade ®} + Dexamethasone) for Patients With Newly Diagnosed Multiple Myeloma
The purpose of the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination.
Read the detailed description
The purpose of the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination.
All of these drugs - vorinostat, bortezomib, lenalidomide and dexamethasone, are approved by the FDA (U.S. Food and Drug Administration). They have not been approved in this combination for use in your type of cancer or any other type of cancer. Vorinostat is approved for treatment of patients with a different type of cancer (Cutaneous T-Cell Lymphoma). Bortezomib is currently approved for the treatment of multiple myeloma. Lenalidomide is currently approved for the treatment of certain types of myelodysplastic syndrome (another form of cancer affecting the blood) and for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma.
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib, Lenalidomide, Dexamethasone, Vorinostat
- Keywords
- Multiple Myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
1.3mg/m² given IV or subcutaneously
LenalidomideDrug
Also called Revlimid
25 mg given PO
DexamethasoneDrug
Also called Decadron
20 mg given PO
VorinostatDrug
Also called Zolinza
100, 200, or 300 mg given PO
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib, lenalidomide, dexamethasone, vorinostat | Experimental | Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11; lenalidomide by mouth once a day on days 1-14; dexamethasone by mouth once a day on days 1, 2, 4, 5, 8, 9, 11, and 12; and vorinostat by mouth on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After 8 courses, patients may receive maintenance therapy comprising lenalidomide by mouth once a day on days 1-21, dexamethasone by mouth once a day on days 1, 2, 8, and 9, and bortezomib IV over 3-5 seconds or subcutaneously on days 1 and 8. Courses may repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of vorinostat in combination with lenalidomide, bortezomib, and dexamethasone.
Measured: Every 3 weeks
Secondary outcomes (1)
Efficacy by standard myeloma measurements (SPEP, UPEP [urine protein electrophoresis], bone marrow)
Measured: Every 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2009 (estimated)
- Study start15 Jan 2010
- Primary completion5 Aug 2021
- Study completion5 Aug 2021
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 Emory UniversityThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Celgene Corporation
- Responsible party
- Principal investigator, Jonathan Kaufman, Emory University
- Investigators
- Jonathan Kaufman, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01038388
- Sponsor's protocol ID
- IRB00017528
- Other IDs
- 1591, RV-MM-PI-0420
- Status last verified
- Nov 2021
- First submitted
- 7 Jul 2009
- Last updated
- 3 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial Evaluating the Safety and Efficacy of Vorinostat (Zolinza ®) + RVD (Lenalidomide {Revlimid ®} + Bortezomib {Velcade ®} + Dexamethasone) for Patients With Newly Diagnosed Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01038388
- Acronym / sponsor ID
- IRB00017528
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Celgene Corporation
- Study start
- 15 Jan 2010 (actual)
- Primary completion
- 5 Aug 2021 (actual)
- Study completion
- 5 Aug 2021 (actual)
- First posted
- 24 Dec 2009 (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 the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination.
Detailed description
The purpose of the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination.
All of these drugs - vorinostat, bortezomib, lenalidomide and dexamethasone, are approved by the FDA (U.S. Food and Drug Administration). They have not been approved in this combination for use in your type of cancer or any other type of cancer. Vorinostat is approved for treatment of patients with a different type of cancer (Cutaneous T-Cell Lymphoma). Bortezomib is currently approved for the treatment of multiple myeloma. Lenalidomide is currently approved for the treatment of certain types of myelodysplastic syndrome (another form of cancer affecting the blood) and for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat 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 |
|---|---|---|
| Bortezomib, lenalidomide, dexamethasone, vorinostat | Experimental | Drug: Bortezomib, Drug: Lenalidomide, Drug: Dexamethasone, Drug: VorinostatPatients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11; lenalidomide by mouth once a day on days 1-14; dexamethasone by mouth once a day on days 1, 2, 4, 5, 8, 9, 11, and 12; and vorinostat by mouth on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, patients may receive maintenance therapy comprising lenalidomide by mouth once a day on days 1-21, dexamethasone by mouth once a day on days 1, 2, 8, and 9, and bortezomib IV over 3-5 seconds or subcutaneously on days 1 and 8. Courses may repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Multiple Myeloma Diagnosis: Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria (ALL 3 REQUIRED):
- Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma.
- Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. One week must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and one week have passed since the last date of therapy.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international unit (mIU)/mL 10 - 14 days prior to therapy and repeated again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
Key exclusion criteria (19 listed)
- Patient has ≥ Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
- Renal insufficiency (serum creatinine levels > 2.5 mg/dL).
- Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/mm³).
- Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm³. Growth factors may not be used to meet ANC eligibility criteria.
- Subjects with a hemoglobin < 8.0 g/dL.
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 |
|---|---|---|
| BortezomibAlso: Velcade1.3mg/m² given IV or subcutaneously | Drug | Bortezomib, lenalidomide, dexamethasone, vorinostat |
| LenalidomideAlso: Revlimid25 mg given PO | Drug | Bortezomib, lenalidomide, dexamethasone, vorinostat |
| DexamethasoneAlso: Decadron20 mg given PO | Drug | Bortezomib, lenalidomide, dexamethasone, vorinostat |
| VorinostatAlso: Zolinza100, 200, or 300 mg given PO | Drug | Bortezomib, lenalidomide, dexamethasone, vorinostat |
Primary outcome
To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of vorinostat in combination with lenalidomide, bortezomib, and dexamethasone.
Time frame: Every 3 weeks
1 secondary outcome
Efficacy by standard myeloma measurements (SPEP, UPEP [urine protein electrophoresis], bone marrow)
Time frame: Every 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
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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.
Jonathan Kaufman, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bortezomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Emory University 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 20 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 3 Nov 2021. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of vorinostat in combination with lenalidomide, bortezomib, and dexamethasone. (time frame: Every 3 weeks). 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 3 Nov 2021.