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Light Chain Deposition DiseasePhase 1NCT01533194

Viral Therapy in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase 1 study testing Diagnostic Laboratory Biomarker Analysis and Wild-type Reovirus in people with Light Chain Deposition Disease and Refractory Plasma Cell Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This pilot phase I trial studies the side effects and the best dose of giving viral therapy to patients with relapsed or refractory multiple myeloma. Viral therapy, such as wild-type reovirus, may be able to kill cancer cells without damaging normal cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Diagnostic Laboratory Biomarker Analysis and Wild-type Reovirus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Apr 2012to Feb 2015
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

  • Patient must have relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria for symptomatic myeloma (although new or worsening end-organ damage is not required to be eligible) as defined below:
  • Presence of ≥ 10% clonal bone marrow plasma cells
  • Presence of serum and/or urinary measurable monoclonal protein or light chains
  • Evidence of any end-organ damage criteria listed below [at any time] attributed to the patient's myeloma:
  • Hypercalcemia: Serum calcium > 11.5 mg/dL
  • Renal insufficiency: Serum creatinine > 2 mg/dL
Show all 42Show fewer
  • Anemia > 2 g/dL below the lower limit of normal or a hemoglobin value < 10 g/dL
  • Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures
  • Subject must have measurable disease defined as any of the following:
  • Serum monoclonal protein > 500 mg/dL by protein electrophoresis
  • > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin free light chain ≥ 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Patients must have received at least one prior antineoplastic therapy and must have progressed
  • No standard therapy is available or patient declines such options
  • Prior autologous and/or allogeneic transplant is permitted although transplant must have occurred greater than 90 days prior to registration
  • Adverse events from prior therapy must have recovered to no greater than grade 1 with the exception of grade 2 neuropathy
  • Prior radiation is permitted; however, at least 4 weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all radiation-associated toxicities to no greater than grade 1 at the time of registration
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%); patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count (ANC) ≥ 1,000/μL
  • Platelet count ≥ 50,000/μL
  • Hemoglobin > 8 g/dL
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times the institutional upper limit of normal.
  • Able to understand and willing to sign a written informed consent document
  • Patients must be able to avoid direct contact with pregnant or nursing women, infants, and immunocompromised individuals during the five days of Reolysin treatment and for two days after
  • Patients must not have known immunodeficiency virus (HIV) infection or active hepatitis B or C infections
  • For patients with a history of congestive heart failure, systolic cardiac function must be assessed at screening and left ventricular ejection fraction (LVEF) ≥ 50%
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to starting therapy and prior to beginning another course (if applicable)
  • FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • The patient must be willing to comply with fertility requirements as below:
  • Male patients must agree to use an adequate method of contraception for the duration of the study and for 90 days afterwards
  • Female patients must be either postmenopausal, free from menses ≥ 2 years, surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from heterosexual activity starting with screening and for 90 days afterwards
  • Patients must agree not to donate blood or sperm/ova during the course of taking protocol therapy and for at least 4 weeks after stopping treatment
  • No patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
  • Patients may be receiving concomitant therapy with bisphosphonates and low-dose corticosteroids (e.g., prednisone up to but no more than 10 mg by mouth daily or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment
  • No patients who are receiving any other investigational agents
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study
  • No patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation
  • No POEMS syndrome
  • No concurrent use of complementary or alternative medicines that, in the opinion of the principal investigator, would confound the interpretation of toxicities and/or antitumor activity of the study drug

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase 1 Study of Reolysin Alone in Patients With Relapsed or Refractory Multiple Myeloma

This pilot phase I trial studies the side effects and the best dose of giving viral therapy to patients with relapsed or refractory multiple myeloma. Viral therapy, such as wild-type reovirus, may be able to kill cancer cells without damaging normal cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine safety and tolerability of Reolysin in patients with relapsed multiple myeloma.

II. Obtain evidence of Reovirus replication by immunohistochemical co-localization of Reovirus and tubulin staining in marrow clot sections obtained on cycle 1 day 8.

SECONDARY OBJECTIVES:

  1. Obtain preliminary data on response as determined by International Myeloma Working Group criteria after infusion of Reolysin as a single agent. (Clinical) II. Obtain pilot overall and progression free survival data for all treated patients. (Clinical) III. Assess neutralizing anti-reovirus assay (NARA) results on days 1, 8, 15, and once days 22-28 during cycle 1. (Correlative) IV. Assess feasibility of staining for RAF/MEK/ERK in CD138+ cells using marrow clot sections obtained from pre-treatment specimen. (Correlative) V. Cryopreserve PBMCs for future ancillary studies focused initially on lymphocyte subset(s) and myeloid derived suppressor cell changes after Reolysin infusion during cycle 1. (Correlative) VI. Cryopreserve CD138+-selected cells at screening and after treatment for future ancillary studies of genetic and epigenetic changes focused in part on endoplasmic reticulum (ER) stress. (Correlative)

OUTLINE: This is a dose-escalation study.

Patients receive wild-type reovirus IV over 60 minutes on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspirate at baseline and periodically during study for RAF/MEK/ERK expression and wild-type reovirus replication analysis by immunohistochemistry. Blood and cryopreserved CD138+ selected cell samples are also collected for future ancillary studies.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Diagnostic Laboratory Biomarker Analysis, 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.

  • Diagnostic Laboratory Biomarker AnalysisOther

    Correlative studies

  • Wild-type ReovirusBiological

    Also called Reolysin

    Given IV

Study groups in NCT01533194
Study groupRoleWhat they receive
Treatment (wild-type reovirus)ExperimentalPatients receive wild-type reovirus IV over 60 minutes on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Receives: Other: Diagnostic Laboratory Biomarker Analysis; Biological: Wild-type Reovirus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Associated adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria and tolerability of wild-type reovirus

    The number and severity of toxicity incidents will indicate the level of tolerance for Reolysin in the treatment of relapsed/refractory multiple myeloma. Toxicities will be evaluated using the CTCAE v. 4 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

    Measured: Up to 4 weeks post-treatment

  2. Maximum-tolerated dose level

    The number and severity of toxicity incidents will indicate the level of tolerance for Reolysin in the treatment of relapsed/refractory multiple myeloma. Toxicities will be evaluated using the CTCAE v. 4 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

    Measured: 28 days

Secondary outcomes (4)

  1. Duration of response

    Defined as the duration from first observation of partial response to the time of disease progression (taking as a reference for progressive disease the smallest measurements recorded since treatment started), with deaths due to other causes other than progression censored. This includes only patients with confirmed responses, and the date at which the response status was first observed rather than the date of confirmation is used as the start date.

    Measured: Up to 2 years

  2. Objective response rate

    Will evaluate clinical benefit endpoint described as that portion of patients experiencing CR, VGPR, or PR. The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.

    Measured: Up to 4 weeks post-treatment

  3. Progression-free survival

    Measured: From start of treatment to disease progression or death, regardless of cause of death, whichever comes first, assessed up to 2 years

  4. Time to progression

    Measured: Time from the start of the treatment until the criteria for disease progression are met, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

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
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01533194
Sponsor's protocol ID
NCI-2012-00248
Other IDs
NCI-2012-00248, CDR0000724857, 2011C0141, 9030, OSU 11148, 9030, P30CA016058, U01CA076576
Status last verified
Dec 2014
First submitted
11 Feb 2012
Last updated
15 Apr 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Diagnostic Laboratory Biomarker Analysis and Wild-type Reovirus in people with Light Chain Deposition Disease and Refractory Plasma Cell Myeloma, run by National Cancer Institute (NCI) 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 42 inclusion and 0 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 15 Apr 2015. 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?

Associated adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria and tolerability of wild-type reovirus (time frame: Up to 4 weeks post-treatment). 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?

On the ClinicalTrials.gov record for NCT01533194.

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 15 Apr 2015.

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