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Recurrent Plasma Cell MyelomaPhase 1NCT03605719

Dexamethasone, Carfilzomib, & Nivolumab With Pelareorep for Relapsed/Refractory Multiple Myeloma

A Phase 1 study testing Carfilzomib, Dexamethasone and Nivolumab in people with Recurrent Plasma Cell Myeloma, run by Emory University at 2 sites 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 phase I trial studies the side effects and best dose of wild-type reovirus (pelareorep) when given together with dexamethasone, carfilzomib, and nivolumab in treating patients with multiple myeloma that has come back (relapsed). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Plasma Cell Myeloma
What is being tested?
Carfilzomib, Dexamethasone and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
2 sitesUnited States
Study dates
24 Oct 2018to 10 Oct 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

  • Patient must have multiple myeloma that fits or did fit International Myeloma Working Group (IMWG) diagnostic criteria
  • In arm 3 but not for arms 1 or 2, patients must have measurable disease defined as any of the following:
  • Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis
  • ≥ 200 mg of monoclonal protein in the urine on screening 24-hour electrophoresis
  • If no m-spike is present, involved serum immunoglobulin free light chain ≥ 100 mg/L AND an abnormal serum light chain ratio (< 0.26 or > 1.65)
  • Progressive disease or clinical relapse at the time of study entry as defined by IMWG
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  • Arm ONE only: Patients must be carfilzomib naive and have received ≥ 2 prior lines of therapy and must have included an IMiD, proteasome inhibitor, and anti-cluster of differentiation 38 (CD38) antibody as defined below
  • IMiD exposure: At least 1 cycle of prior treatment unless stopped due to intolerance
  • CD38 antibody exposure: At least 4 doses unless stopped due to intolerance
  • Proteasome inhibitor exposed: At least 1 cycle of prior treatment unless stopped due to intolerance
  • Arm TWO and THREE only: Patients must have received ≥ 3 prior lines of therapy and must have included an immunomodulatory imide drug (IMiD), proteasome inhibitor, and anti-CD38 antibody as above along with evidence of proteasome inhibitor resistance defined as less than or equal to stable disease with prior treatment with a proteasome inhibitor containing regimen at moderate doses defined as carfilzomib 27+ mg/m²/week (wk), bortezomib 1.3+ mg/m²/wk subcutaneously (SQ) or IV, or ixazomib 3+ mg/wk orally (PO)
  • Both men and women of all races and ethnic groups are eligible for this study
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%) is required for eligibility. Those patients with lower performance status based solely on bone pain secondary to multiple myeloma are eligible
  • Prior autologous and/or allogeneic transplant is permitted although transplant must have occurred greater than 90 days prior to registration
  • Absolute neutrophil count (ANC) > 1000/µL for at least one week prior to screening
  • Platelet count ≥ 70,000 and platelet transfusion independent for one week prior to screening (platelets allowed to be down to 50,000 if > 50% plasma cells on screening aspirate or core biopsy)
  • Estimated creatinine clearance ≥ 30 mL/min as defined by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Cockcroft-Gault
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3x the institutional upper limit of normal
  • Left ventricular ejection fraction ≥ 40%
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy. The effects of pelareorep and nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential 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. 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. Female of childbearing potential (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 7 months 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 5 months after last treatment in all patients
  • Patients must agree not to donate blood, sperm/ova while taking protocol therapy and for at least 7 months after stopping treatment (for males) and 5 months after stopping treatment (for females)
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Who cannot join

  • Known human immunodeficiency virus (HIV) infection or active hepatitis B or C due to risk of viral infectivity of pelareorep
  • Known pulmonary hypertension
  • Patients who are receiving any other anti-myeloma investigational agents
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, primary amyloidosis (AL amyloidosis), and Waldenstrom macroglobulinemia
  • Patients who have had anti-myeloma treatment, radiotherapy, plasmapheresis, or major surgery (as defined by the investigator) within 2 weeks prior to cycle 1 day 1 of 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
  • Uncontrolled 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 because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to protocol treatment of the mother, breastfeeding should be discontinued

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: PD1 Blockade and Oncolytic Virus in Relapsed Multiple Myeloma

This phase I trial studies the side effects and best dose of wild-type reovirus (pelareorep) when given together with dexamethasone, carfilzomib, and nivolumab in treating patients with multiple myeloma that has come back (relapsed). Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. A virus, called pelareorep, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Giving dexamethasone, carfilzomib, and nivolumab with pelareorep may work better in treating patients with multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Identify maximum tolerated dose of pelareorep in combination with other antineoplastic agents.

II. Identify whether the combination of carfilzomib and nivolumab lead to a safety profile different than what has been reported with either agent independently.

SECONDARY OBJECTIVES:

  1. Assess the relative roles of immune-mediated and direct cytotoxic myeloma cell killing.

II. Understand the clinical benefit of nivolumab in programmed death-ligand 1 (PD-L1) positive multiple myeloma (MM) cells.

OUTLINE: This is a dose-escalation study of pelareorep. Patients are assigned to 1 of 3 arms.

ARM 1: Patients receive dexamethasone intravenously (IV) on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM 3 (expansion cohort): Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for a minimum of 4 weeks once off treatment or at least 100 days after the last nivolumab dose, then every 6 months after.

Being tested
Carfilzomib, Dexamethasone, Nivolumab, Pelareorep
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV

  • DexamethasoneDrug

    Also called Decadron, Hexadrol, Ozurdex

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • PelareorepBiological

    Also called Reolysin, Wild-type Reovirus

    Given IV

Study groups in NCT03605719
Study groupRoleWhat they receive
Arm 1ExperimentalPatients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carfilzomib; Drug: Dexamethasone; Biological: Nivolumab
Arm 2ExperimentalPatients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carfilzomib; Drug: Dexamethasone; Biological: Nivolumab; Biological: Pelareorep
Arm 3 (expansion)ExperimentalPatients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carfilzomib; Drug: Dexamethasone; Biological: Nivolumab; Biological: Pelareorep

What is being measured

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

  1. Dose-limiting toxicity (DLT) of 4-drug regimen evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

    A DLT is defined as one of the following toxicities:

    • Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/µL) lasting 5 days or more.
    • Grade 3 to 4 thrombocytopenia associated with bleeding requiring platelet transfusion
    • Cardiac dysfunction: Grade > 3 left ventricular systolic dysfunction or grade > 2 myocarditis
    • Any grade 3-4 treatment-emergent non-hematologic adverse event (AE) clearly unrelated to the underlying disease and considered to be at least possibly related to protocol therapy

    Measured: Up to 28 days after cycle 1 start

  2. Maximum tolerated dose (MTD) of 4-drug regimen

    The Escalation with Overdose Control (EWOC) design will be used to identify the MTD.

    Measured: Up to 28 days after cycle 1 start

  3. DLT of 3-drug regimen evaluated according to NCI CTCAE version 5.0

    A DLT is defined as one of the following toxicities:

    • Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/µL) lasting 5 days or more.
    • Grade 3 to 4 thrombocytopenia associated with bleeding requiring platelet transfusion
    • Cardiac dysfunction: Grade > 3 left ventricular systolic dysfunction or grade > 2 myocarditis
    • Any grade 3-4 treatment-emergent non-hematologic adverse event (AE) clearly unrelated to the underlying disease and considered to be at least possibly related to protocol therapy

    Measured: Up to 28 days after cycle 1 start

Secondary outcomes (3)

  1. Time to progression

    Defined as the time from start of protocol therapy until the criteria for disease progression are met. Patients who are either lost to follow-up, die or who begin alternative treatments prior to progression, will have their data censored as of the date considered to be lost to follow-up, date of death, or the first day of alternative therapy.

    Measured: From start of protocol therapy up to 3 years

  2. Progression-free survival

    Defined as the time from start of protocol therapy to disease progression or death from any cause, censoring patients without an event at time of last clinical assessment.

    Measured: From start of protocol therapy up to 3 years

  3. Overall survival

    Defined as the time from start of protocol therapy to death, censoring patients who are alive at last follow-up.

    Measured: From start of protocol therapy 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.

  1. First posted30 Jul 2018
  2. Study start24 Oct 2018
  3. Primary completion10 Oct 2022
  4. Study completion10 Oct 2022

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03605719
Sponsor's protocol ID
IRB00104234
Other IDs
NCI-2018-01217, Winship4398-18, P30CA138292
Status last verified
Oct 2023
First submitted
20 Jul 2018
Last updated
6 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carfilzomib, Dexamethasone and Nivolumab in people with Recurrent Plasma Cell Myeloma, run by Emory University at 2 sites 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 27 inclusion and 7 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 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Dose-limiting toxicity (DLT) of 4-drug regimen evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (time frame: Up to 28 days after cycle 1 start). The study lists 3 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 NCT03605719.

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 6 Oct 2023.

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