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Trial record 3 of 16 for:    hofmeister

Viral Protein Production After Dexamethasone, Wild-Type Reovirus, and Carfilzomib in Treating Patients With Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02101944
First received: March 28, 2014
Last updated: November 21, 2014
Last verified: November 2014

March 28, 2014
November 21, 2014
September 2014
January 2017   (final data collection date for primary outcome measure)
  • Reovirus replication as measured by reovirus capsid protein production [ Time Frame: Day 1 of first course ] [ Designated as safety issue: No ]
  • Reovirus replication as measured by reovirus capsid protein production [ Time Frame: Day 9 of first course ] [ Designated as safety issue: No ]
  • Adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
  • Tolerability (number and severity of toxicity incidents) of combination carfilzomib and wild-type reovirus assessed by CTCAE version 4 [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
    Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
  • Number of patients who required dose modifications and/or dose delays in subsequent cycles [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
  • Proportion of patients who go off treatment due to adverse reactions or refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
  • Reovirus replication as measured by reovirus capsid protein production [ Time Frame: Days 1 and 9 of first course ] [ Designated as safety issue: No ]
  • Adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
  • Tolerability (number and severity of toxicity incidents) of combination carfilzomib and wild-type reovirus assessed by CTCAE version 4 [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
    Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
  • Number of patients who required dose modifications and/or dose delays in subsequent cycles [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
  • Proportion of patients who go off treatment due to adverse reactions or refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT02101944 on ClinicalTrials.gov Archive Site
  • Number and percentage of subjects experiencing objective response [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    Summary statistics will be computed for baseline biomarkers. The absolute and percent change from baseline will be calculated for each subsequent measurement. Summary statistics will be computed for each collection time point. The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.
  • Clinical benefit endpoint described as that portion of patients experiencing complete response (CR), very good partial response (VGPR), or partial response (PR) [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.
  • Duration of response [ Time Frame: Duration from first observation of partial response to the time of disease progression, up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.
  • Progression free survival [ Time Frame: Duration from start of treatment to disease progression or death, regardless of cause of death, whichever comes first, up to 2 years ] [ Designated as safety issue: No ]
    This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.
  • Time to progression [ Time Frame: Time from the start of the treatment until the criteria for disease progression are met, up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.
  • Number and percentage of subjects experiencing objective response [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    Summary statistics will be computed for baseline biomarkers. The absolute and percent change from baseline will be calculated for each subsequent measurement. Summary statistics will be computed for each collection time point. The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.
  • Clinical benefit endpoint described as that portion of patients experiencing complete response (CR), very good partial response (VGPR), or partial response (PR) [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.
  • Duration of response [ Time Frame: Duration from first observation of partial response to the time of disease progression, up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.
  • Progression free survival [ Time Frame: Duration from start of treatment to disease progression or death, regardless of cause of death, whichever comes first, up to 6 months ] [ Designated as safety issue: No ]
    This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.
  • Time to progression [ Time Frame: Time from the start of the treatment until the criteria for disease progression are met, up to 4 weeks post treatment ] [ Designated as safety issue: No ]
    This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.
Immunologic correlative markers [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Will descriptively summarize the continuous markers quantitatively. Patterns of change in the longitudinal data on these markers will be evaluated in this manner for each of the correlative outcomes of interest. Appropriate transformations of the various correlative markers will be used in the presence of skewed data distributions. Multiple comparison corrections will not be used for these secondary correlative analyses. Peripheral blood will be collected at pretreatment on day 1, day 2, and day 9, 15 and once during days 22-28 of cycle 1, and day 1 of cycle 2 and each successive cycle.
Immunologic correlative markers [ Time Frame: Up to day 28 ] [ Designated as safety issue: No ]
Will descriptively summarize the continuous markers quantitatively. Patterns of change in the longitudinal data on these markers will be evaluated in this manner for each of the correlative outcomes of interest. Appropriate transformations of the various correlative markers will be used in the presence of skewed data distributions. Multiple comparison corrections will not be used for these secondary correlative analyses.
 
Viral Protein Production After Dexamethasone, Wild-Type Reovirus, and Carfilzomib in Treating Patients With Multiple Myeloma
Pilot Trial Evaluating Viral Protein Production From the Combination of Reolysin and Carfilzomib in Multiple Myeloma

This pilot clinical trial studies the activity of dexamethasone, wild-type reovirus, and carfilzomib in patients with multiple myeloma and viral protein production following treatment. Drugs used in chemotherapy, such as dexamethasone and carfilzomib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A virus called wild-type reovirus may be able to kill cancer cells without damaging normal cells and seems to work best when given with chemotherapy. Giving wild-type reovirus with chemotherapy may be a more active treatment than chemotherapy alone.

PRIMARY OBJECTIVES:

I. Determine safety and tolerability of reolysin (wild-type reovirus), carfilzomib and dexamethasone in patients with relapsed multiple myeloma.

II. Obtain evidence of reovirus protein production by immunohistochemical localization of reoviral capsid protein in myeloma cells from bone marrow biopsies obtained on cycle 1 day 9.

SECONDARY OBJECTIVES:

I. Obtain preliminary data on response as determined by International Myeloma Working Group criteria after protocol therapy.

II. Obtain pilot overall and progression free survival data for all treated patients.

III. Assess cytokine arrays of peripheral blood obtained on days 1, 2 and 9 to obtain exploratory data regarding inflammatory cytokine concentrations and their correlation with response.

IV. Cryopreserve marrow aspirates obtained cycle 1 day 1 and all subsequent marrow aspirates while on trial for future studies of genetic and epigenetic changes focused in part on endoplasmic reticulum (ER) stress, autophagy and reovirus resistance studies.

OUTLINE:

Patients receive dexamethasone intravenously (IV), carfilzomib IV over 10 minutes, and wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 6 months.

Interventional
Not Provided
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Refractory Plasma Cell Myeloma
  • Drug: Dexamethasone
    Given IV
    Other Name: DM
  • Drug: Carfilzomib
    Given IV
    Other Names:
    • Kyprolis
    • PR-171
  • Biological: Wild-type Reovirus
    Given IV
    Other Names:
    • REOLYSIN
    • Reolysin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Treatment (dexamethasone, wild-type reovirus, carfilzomib)
Patients receive dexamethasone IV, carfilzomib IV over 10 minutes, and wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Dexamethasone
  • Drug: Carfilzomib
  • Biological: Wild-type Reovirus
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
Not Provided
January 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient must have relapsed or refractory myeloma that fits or did fit International Myeloma Working Group (IMWG) diagnostic criteria for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:

    • Presence of 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 or
      • Renal insufficiency: serum creatinine > 2 mg/dL
      • 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
  • Patients 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 screening 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 an immunomodulatory drug (IMiD) and proteasome inhibitor, and must be progressing; prior autologous and/or allogeneic transplant is permitted although transplant must have occurred greater than 90 days prior to registration
  • Both men and women of all races and ethnic groups are eligible for this study
  • In the expansion cohort only, 3 patients can have progressed while receiving a carfilzomib-containing regimen in the past
  • Prior radiation is permitted; however, at least 2 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
  • Patients with expected carfilzomib sensitive disease, Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) is required for eligibility; those patients with expected carfilzomib sensitive disease with lower performance status based solely on bone pain secondary to multiple myeloma are eligible; patients with myeloma-related pain or other disease-related morbidities equivalent to > grade 2 toxicity or ECOG performance status > 1 expected to be carfilzomib refractory are ineligible
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 50,000/uL
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the institutional upper limit of normal
  • Ability to understand and the willingness 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 days of reolysin treatment and for two days after
  • Patients must not have known human immunodeficiency virus (HIV) infection or active hepatitis B or C infections
  • Systolic cardiac function will be assessed at screening if clinically indicated by history and physical; only patients with left ventricular ejection fraction (LVEF) >= 50% will be eligible for enrollment
  • 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 cycle (if applicable)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting 28 days prior to starting the study until at least 90 days following discontinuation of the trial therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • 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, sperm/ova during the course of taking protocol therapy and for at least 4 weeks after stopping treatment

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 2 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
  • Patients who are receiving any other therapeutic investigational agents
  • Patients previously treated on clinical trial with reolysin
  • 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; breastfeeding should be discontinued
  • 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
  • Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS) syndrome
  • 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
Both
18 Years and older
No
United States
 
NCT02101944
NCI-2014-00643, NCI-2014-00643, 2014C0091, NCI-9603, 14031, OSU-14031, 9603, UM1CA186712, U01CA076576, P30CA016058
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Craig Hofmeister Ohio State University
National Cancer Institute (NCI)
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP