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Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma (MUKeleven)

This study is currently recruiting participants.
Verified June 2017 by Gordon Cook, The Leeds Teaching Hospitals NHS Trust
Sponsor:
ClinicalTrials.gov Identifier:
NCT03015922
First Posted: January 10, 2017
Last Update Posted: June 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Myeloma UK
Oncolytics Biotech
Celgene Corporation
Information provided by (Responsible Party):
Gordon Cook, The Leeds Teaching Hospitals NHS Trust
  Purpose
This study will recruit patients currently receiving either lenalidomide or pomalidomide whose disease is relapsing. This is a dose escalation study and the aim is to determine the maximum tolerated dose (MTD) of REOLYSIN® that can be given in combination with lenalidomide or pomalidomide. The study will also investigate the safety, side effects and effectiveness of this treatment combination. Pomalidomide and lenalidomide will be evaluated separately as two separate groups.

Condition Intervention Phase
Multiple Myeloma Drug: Lenalidomide or Pomalidomide Biological: REOLYSIN Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: VIRel: Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma - A Phase I Study to Assess the Safety and Tolerability of REOLYSIN® (Pelareorep) in Combination With Lenalidomide or Pomalidomide

Resource links provided by NLM:


Further study details as provided by Gordon Cook, The Leeds Teaching Hospitals NHS Trust:

Primary Outcome Measures:
  • Dose-limiting toxicities [ Time Frame: After cycle 1 (28 days) of treatment. Assessed in real-time for each patient to inform dose escalation decisions. ]
    Dose-limiting toxicities (DLTs), within the first cycle (until cycle 2, day 1), in order to establish the Maximum Tolerated Dose (MTD) of REOLYSIN® in combination with lenalidomide or pomalidomide, in two separate groups of participants.


Secondary Outcome Measures:
  • Safety profile of REOLYSIN® and lenalidomide [ Time Frame: Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months. ]
    Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.

  • Safety profile of REOLYSIN® and pomalidomide [ Time Frame: Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months. ]
    Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.

  • Toxicity profile of REOLYSIN® and lenalidomide [ Time Frame: Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months. ]
    Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.

  • Toxicity profile of REOLYSIN® and pomalidomide [ Time Frame: Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months. ]
    Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.

  • Response rate (stable disease or better) after 6 cycles of therapy [ Time Frame: Data will be collected from each patient after they have received 6 cycles of therapy, if this stage is reached. 6 cycles are expected to take 24 weeks to complete. ]
    Measured only in patients treated at the maximum tolerated dose

  • Maximum response within 6 cycles of therapy [ Time Frame: Assessed for each patient after they have received 6 cycles of treatment. 6 cycles are expected to take 24 weeks to complete. ]
    Measured only in patients treated at the maximum tolerated dose

  • Maximum response overall [ Time Frame: Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months. ]
    Measured only in patients treated at the maximum tolerated dose

  • Time to maximum response [ Time Frame: Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months. ]
    Measured only in patients treated at the maximum tolerated dose

  • Progression-free survival [ Time Frame: Calculated for each patient from the date of registration up to first documented evidence of disease progression or death. Assessed up to 27 months. ]
    Measured only in patients treated at the maximum tolerated dose. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression free.

  • Overall survival [ Time Frame: Calculated for each patient from the date of registration to death. Assessed up to 27 months. ]
    Measured only in patients treated at the maximum tolerated dose. Participants who have not died at the time of analysis will be censored at the last date they were known to be alive.


Other Outcome Measures:
  • Immune response biomarker profile of REOLYSIN and lenalidomide administered in combination [ Time Frame: This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months. ]
    Biomarker profiling of the combination treatment

  • Immune response biomarker profile of REOLYSIN® and pomalidomide administered in combination [ Time Frame: This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months. ]
    Biomarker profiling of the combination treatment


Estimated Enrollment: 44
Actual Study Start Date: June 5, 2017
Estimated Study Completion Date: October 1, 2020
Estimated Primary Completion Date: July 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide or pomalidomide, plus REOLYSIN

Lenalidomide capsules, oral, maximum 10mg daily on days 1-21 of 28-day cycles. OR Pomalidomide capsules, oral, maximum 1mg daily on days 1-21 of 28-day cycles.

Plus (all patients):

REOLYSIN® , intravenous infusion, maximum 3x10^10 TCID50 on days 1, 8, 15 and 22 of 28-day cycles.

Drug: Lenalidomide or Pomalidomide
Patients will received either lenalidomide or pomalidomide, depending on which drug they were receiving prior to the trial (they will receive the same as before).
Biological: REOLYSIN
Patients will receive Reolysin alongside either lenalidomide or pomalidomide
Other Names:
  • Pelareorep
  • Reovirus

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with symptomatic multiple myeloma (according to IMWG 2014 criteria)
  • Evaluable disease by modified IMWG criteria (i.e. by abnormal serum M protein, urinary M protein or serum free light chain assays)
  • Currently receiving either lenalidomide or pomalidomide therapy, alone or in combination with other myeloma therapy, with evidence of serological or clinical disease progression as defined by IMWG criteria (2011)
  • Life expectancy of ≥ 3 months
  • ECOG performance status of ≤2
  • Required laboratory values within 14 days prior to dose allocation:
  • Absolute neutrophil count ≥ 1.0 x10^9 /L. (growth factor support is not permitted)
  • Platelet count ≥ 70 x 10^9/L. (platelet support is not permitted; platelets < 70 but ≥ 25 acceptable if bone marrow is > 50% infiltrated by MM)
  • Haemoglobin ≥ 8 g/dL. Blood support is permitted
  • Serum bilirubin ≤ 2 x upper limit of normal (ULN)
  • ALT or AST ≤ 2.5 x ULN
  • Serum creatinine ≤ 2 x ULN
  • Corrected calcium ≤ 2.8 mmol/l
  • Negative HIV and viral (B and C) hepatitis test result within 14 days prior to dose allocation
  • Able to give informed consent and willing to follow trial protocol
  • Aged 18 years or over
  • All participants must agree to follow the Celgene Pregnancy Prevention Programme (PPP) and participate in the counselling associated with this:
  • Females of childbearing potential (FCBP) must agree to utilise two reliable forms of contraception simultaneously or practice complete abstinence for at least for 28 days prior to starting trial treatment, during the trial and for at least 28 days after trial treatment discontinuation, and even in case of dose interruption, and must agree to Celgene PPP pregnancy testing during this timeframe
  • Females must agree to abstain from breastfeeding during trial participation and 28 days after trial drug discontinuation
  • Males must agree to use a latex condom during any sexual contact with FCBP (or must practice complete abstinence) during the trial, including during dose interruptions and for 28 days following discontinuation from this trial even if he has undergone a successful vasectomy
  • Males must also agree to refrain from donating semen or sperm while on pomalidomide including during any dose interruptions and for 28 days after discontinuation from this trial
  • All participants must agree to refrain from donating blood while on trial drug including during dose interruptions and for 28 days after discontinuation from this trial

Exclusion Criteria:

  • Non-secretory multiple myeloma
  • Pregnant (positive pregnancy test) in line with the Celgene Pregnancy Prevention Programme or breast feeding
  • Previous anti-tumour therapies including experimental agents, other than lenalidomide or pomalidomide, within 28 days of the start of protocol treatment. Steroid therapy is permitted, but must be stopped 48 hours prior to cycle 1 day 1
  • Concurrent or previous malignancies (<12 months post end of treatment) at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer, or incidental histologic findings of prostate cancer (TNM stage T1a or 1b). Participants with histories (≥12 months) of other tumours, in remission and not currently on therapy, may be entered
  • System corticosteroid therapy for comorbidities (i.e. medical conditions other than multiple myeloma) that cannot be stopped for the duration of the trial. Topical corticosteroid therapy is not an exclusion criterion.
  • Any history of known hypersensitivity to any of the trial medications or excipients
  • Active symptomatic fungal, bacterial, and/or viral infection
  • Poorly controlled or serious medical or psychiatric illness that, in the Investigator's opinion, is likely to interfere with participation and/or compliance in this clinical trial
  • Patients with significant cardiovascular disease (e.g. history of congestive heart failure requiring therapy (≥ NYHA Class III), presence of severe valvular heart disease, presence of an atrial or ventricular arrhythmia requiring treatment, uncontrolled hypertension, or history of QTc abnormalities)
  • Radiotherapy or major surgery within 4 weeks prior to registration
  • Greater than or equal to grade 2 neuropathy, with or without pain
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03015922


Contacts
Contact: Gordon Cook 0113 343 1477 medmuk11@leeds.ac.uk

Locations
United Kingdom
St James's University Hospital Recruiting
Leeds, United Kingdom
Contact: Christopher Parrish         
Principal Investigator: Christopher Parrish         
Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital Not yet recruiting
Sheffield, United Kingdom
Contact: Andrew Chantry         
Principal Investigator: Andrew Chantry         
Sponsors and Collaborators
University of Leeds
Myeloma UK
Oncolytics Biotech
Celgene Corporation
Investigators
Principal Investigator: Gordon Cook St. James's University Hospital
  More Information

Responsible Party: Gordon Cook, Consultant Haematologist, The Leeds Teaching Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT03015922     History of Changes
Other Study ID Numbers: HM16/118
First Submitted: November 16, 2016
First Posted: January 10, 2017
Last Update Posted: June 14, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Pomalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents