Recurrent Plasma Cell MyelomaPhase 1NCT02514382
Wild-Type Reovirus, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing Bortezomib, Dexamethasone and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by University of Southern California at 1 site in United States.
Trial summary
This phase Ib trial studies the safety and best dose of wild-type reovirus in combination with bortezomib and dexamethasone and to see how well they work in treating patients with multiple myeloma that has returned (relapsed) or does not respond to treatment (refractory). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Bortezomib, Dexamethasone and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Aug 2015to 19 Apr 2022
- 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
- Have relapsed or refractory MM after at least one line of therapy
- Have a confirmed diagnosis of MM with measurable disease, as defined by the presence of monoclonal immunoglobulin protein in serum electrophoreses of at least 0.5 g/dL for immunoglobulin G (IgG) or 0.25 g/dL for IgA, or measurable light chain in serum (100 mg/L) or urinary excretion of at least 200 mg monoclonal light chain per 24 hours
- Have NO continuing acute toxic effects (except alopecia) of any prior chemotherapy, radiotherapy or surgical procedures; all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) grade =< 1; surgery (except minor procedures such as biopsies, IV line placement, etc.) must have occurred at least 28 days prior to study enrollment
- Have received NO anti-cancer therapy within 28 days prior to receiving study drug
- Have received NO radiotherapy within 14 days prior to receiving study drug
- Have an Eastern Cooperative Oncology Group (ECOG) Performance score =< 2
Show all 16Show fewer
- Have a life expectancy of at least 3 months
- Absolute neutrophil count (ANC) >= 1 x 10^9 (International System [SI] units 10^9/L) (with or without filgrastim [G-CSF])
- Platelets >= 50 x10^9 (SI units 10^9/L)
- Serum creatinine =< 2 x upper limit of normal (ULN)
- Bilirubin =< 1.5 x ULN
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x ULN if patients have liver involvement with MM)
- Proteinuria < grade 2
- Have a negative pregnancy test if a female with childbearing potential
- Have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, possible alternative therapies, potential benefits, side effects, risks, and discomforts
- Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests
Who cannot join
- Have a history of or current evidence of intracranial disease; patients with brain metastases must be excluded from this clinical trial
- Be on immunosuppressive therapy or have human immunodeficiency virus (HIV) infection or active hepatitis B or C
- Be a pregnant or breast-feeding woman; female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal; male patients must agree to use effective contraception or be surgically sterile; barrier methods are a recommended form of contraception
- Have clinically significant cardiac disease (New York Heart Association, class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction 1 year prior to study entry, or a known history of grade 2 or higher compromised left ventricular ejection fraction
- Have dementia or altered mental status that would prohibit informed consent
- Have any other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the principal investigator, would make the patient inappropriate for this study
- Have a history of allergic (anaphylactic) sensitivity to bortezomib, boron or mannitol
- Have grade 2 or greater neuropathy at the time of screening
Trial locations and contacts
1 site in 1 country.
United States1 site
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
About this study
Official title: A Phase 1b Study of REOLYSIN® (Reovirus Serotype 3 - Dearing Strain) Combined With Standard Doses of Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
This phase Ib trial studies the safety and best dose of wild-type reovirus in combination with bortezomib and dexamethasone and to see how well they work in treating patients with multiple myeloma that has returned (relapsed) or does not respond to treatment (refractory). A virus, called wild-type reovirus, may be able to infect cancer cells and slow the cancer growth and kill cancer cells. Bortezomib and dexamethasone may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving wild-type reovirus together with bortezomib and dexamethasone may be a better treatment for multiple myeloma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) with the maximum REOLYSIN (wild-type reovirus) dose limited to 4.5 x 10^10 tissue culture infection dose (TCID)50 and the safety profile of REOLYSIN in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (MM). (Phase 1b) II. To further explore the safety and tolerability of the combination and to determine the overall response rate (ORR) (complete response [CR] + partial response [PR]) to REOLYSIN in combination with bortezomib and dexamethasone in patients with relapsed or refractory MM. (Phase 1b Dose Expansion)
SECONDARY OBJECTIVES:
- To determine ORR in the Phase 1b part to the combination at escalating doses.
II. To determine the progression-free survival (PFS) of patients with relapsed or refractory MM treated with REOLYSIN in combination with bortezomib and dexamethasone.
III. To evaluate the effect of REOLYSIN in combination with bortezomib and dexamethasone treatments on overall survival (OS).
IV. To conduct pharmacodynamic studies as described.
OUTLINE: This is a phase Ib, dose-escalation study of wild-type reovirus followed by a phase Ib expansion trial.
Patients receive dexamethasone orally (PO), intravenously (IV), or intramuscularly (IM) and bortezomib subcutaneously (SC) (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.
- Being tested
- Bortezomib, Dexamethasone, Laboratory Biomarker Analysis, Pharmacological Study, Wild-type Reovirus
- 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 [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341
Given SC or IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO, IV, or IM
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
Wild-type ReovirusBiological
Also called Reolysin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dexamethasone, bortezomib, wild-type reovirus) | Experimental | Patients receive dexamethasone PO, IV, or IM and bortezomib SC (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bortezomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Wild-type Reovirus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events assessed by CTCAE version 4.03
The safety of the bortezomib, dexamethasone, and wild-type reovirus combination will be assessed by the evaluation of the type, frequency, and severity of adverse events.
Measured: Up to 30 days post-treatment
Secondary outcomes (1)
ORR
Will determine ORR (CR + PR) in the Phase 1b part to the combination at escalating doses.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2015 (estimated)
- Study start21 Aug 2015
- Primary completion19 Apr 2022
- Study completion19 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Oncolytics Biotech
- Responsible party
- Sponsor
- Investigators
- Kevin Kelly, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02514382
- Sponsor's protocol ID
- 16M-15-2
- Other IDs
- NCI-2015-01069, REO 019, 16M-15-2, P30CA014089
- Status last verified
- Aug 2023
- First submitted
- 30 Jul 2015
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nawrocki ST, Olea J, Villa Celi C, Dadrastoussi H, Wu K, Tsao-Wei D, Colombo A, Coffey M, Fernandez Hernandez E, Chen X, Nuovo GJ, Carew JS, Mohrbacher AF, Fields P, Kuhn P, Siddiqi I, Merchant A, Kelly KR. Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial. Clin Cancer Res. 2023 Dec 15;29(24):5087-5103. doi: 10.1158/1078-0432.CCR-23-0229.
PubMed 37812476
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of REOLYSIN® (Reovirus Serotype 3 - Dearing Strain) Combined With Standard Doses of Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02514382
- Acronym / sponsor ID
- 16M-15-2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Oncolytics Biotech
- Study start
- 21 Aug 2015 (actual)
- Primary completion
- 19 Apr 2022 (actual)
- Study completion
- 19 Apr 2022 (actual)
- First posted
- 3 Aug 2015 (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.
This phase Ib trial studies the safety and best dose of wild-type reovirus in combination with bortezomib and dexamethasone and to see how well they work in treating patients with multiple myeloma that has returned (relapsed) or does not respond to treatment (refractory). A virus, called wild-type reovirus, may be able to infect cancer cells and slow the cancer growth and kill cancer cells. Bortezomib and dexamethasone may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving wild-type reovirus together with bortezomib and dexamethasone may be a better treatment for multiple myeloma.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) with the maximum REOLYSIN (wild-type reovirus) dose limited to 4.5 x 10^10 tissue culture infection dose (TCID)50 and the safety profile of REOLYSIN in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (MM). (Phase 1b) II. To further explore the safety and tolerability of the combination and to determine the overall response rate (ORR) (complete response [CR] + partial response [PR]) to REOLYSIN in combination with bortezomib and dexamethasone in patients with relapsed or refractory MM. (Phase 1b Dose Expansion)
SECONDARY OBJECTIVES:
- To determine ORR in the Phase 1b part to the combination at escalating doses.
II. To determine the progression-free survival (PFS) of patients with relapsed or refractory MM treated with REOLYSIN in combination with bortezomib and dexamethasone.
III. To evaluate the effect of REOLYSIN in combination with bortezomib and dexamethasone treatments on overall survival (OS).
IV. To conduct pharmacodynamic studies as described.
OUTLINE: This is a phase Ib, dose-escalation study of wild-type reovirus followed by a phase Ib expansion trial.
Patients receive dexamethasone orally (PO), intravenously (IV), or intramuscularly (IM) and bortezomib subcutaneously (SC) (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dexamethasone, bortezomib, wild-type reovirus) | Experimental | Drug: Bortezomib, Drug: Dexamethasone, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Biological: Wild-type ReovirusPatients receive dexamethasone PO, IV, or IM and bortezomib SC (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses 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 (16 listed)
- Have relapsed or refractory MM after at least one line of therapy
- Have a confirmed diagnosis of MM with measurable disease, as defined by the presence of monoclonal immunoglobulin protein in serum electrophoreses of at least 0.5 g/dL for immunoglobulin G (IgG) or 0.25 g/dL for IgA, or measurable light chain in serum (100 mg/L) or urinary excretion of at least 200 mg monoclonal light chain per 24 hours
- Have NO continuing acute toxic effects (except alopecia) of any prior chemotherapy, radiotherapy or surgical procedures; all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) grade =< 1; surgery (except minor procedures such as biopsies, IV line placement, etc.) must have occurred at least 28 days prior to study enrollment
- Have received NO anti-cancer therapy within 28 days prior to receiving study drug
- Have received NO radiotherapy within 14 days prior to receiving study drug
Key exclusion criteria (8 listed)
- Have a history of or current evidence of intracranial disease; patients with brain metastases must be excluded from this clinical trial
- Be on immunosuppressive therapy or have human immunodeficiency virus (HIV) infection or active hepatitis B or C
- Be a pregnant or breast-feeding woman; female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal; male patients must agree to use effective contraception or be surgically sterile; barrier methods are a recommended form of contraception
- Have clinically significant cardiac disease (New York Heart Association, class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction 1 year prior to study entry, or a known history of grade 2 or higher compromised left ventricular ejection fraction
- Have dementia or altered mental status that would prohibit informed consent
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: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341Given SC or IV | Drug | Treatment (dexamethasone, bortezomib, wild-type reovirus) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO, IV, or IM | Drug | Treatment (dexamethasone, bortezomib, wild-type reovirus) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (dexamethasone, bortezomib, wild-type reovirus) |
| Pharmacological StudyCorrelative studies | Other | Treatment (dexamethasone, bortezomib, wild-type reovirus) |
| Wild-type ReovirusAlso: ReolysinGiven IV | Biological | Treatment (dexamethasone, bortezomib, wild-type reovirus) |
Primary outcome
Incidence of adverse events assessed by CTCAE version 4.03
Time frame: Up to 30 days post-treatment
The safety of the bortezomib, dexamethasone, and wild-type reovirus combination will be assessed by the evaluation of the type, frequency, and severity of adverse events.
1 secondary outcome
ORR
Time frame: Up to 3 years
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 14 Aug 2023.
- Derived from this study: PubMed 37812476Nawrocki ST, Olea J, Villa Celi C, Dadrastoussi H, Wu K, Tsao-Wei D, Colombo A, Coffey M, Fernandez Hernandez E, Chen X, Nuovo GJ, Carew JS, Mohrbacher AF, Fields P, Kuhn P, Siddiqi I, Merchant A, Kelly KR. Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial. Clin Cancer Res. 2023 Dec 15;29(24):5087-5103. doi: 10.1158/1078-0432.CCR-23-0229.
Related trials for Recurrent Plasma Cell Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1
A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Relapsed or Refractory Multiple Myeloma
RecruitingPhase 2
Study of HBI0101 (NXC-201) CAR-T Therapy in Multiple Myeloma and Light-Chain Amyloidosis
Multiple Myeloma, Refractory to Standard Treatment, Multiple Myeloma, Relapsed
RecruitingPhase 2
Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse
Recurrent Multiple Myeloma, Refractory Multiple Myeloma
Active, not recruitingPhase 1
A Study of JNJ-87562761 in Participants With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma
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.
Kevin Kelly, MD principal investigator
University of Southern California
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, Dexamethasone and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by University of Southern California 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 16 inclusion and 8 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 14 Aug 2023. 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?
Incidence of adverse events assessed by CTCAE version 4.03 (time frame: Up to 30 days post-treatment). 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 NCT02514382, 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 14 Aug 2023; AzTrials last refreshed its copy on 7 Nov 2026.