Condition category
Cancer
Date applied
09/01/2017
Date assigned
11/01/2017
Last edited
15/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation.

Trial website

Contact information

Type

Public

Primary contact

Mrs Debbie Sharratt

ORCID ID

Contact details

University of Leeds
Leeds
LS2 9JT
United Kingdom

Additional identifiers

EudraCT number

2016-001564-11

ClinicalTrials.gov number

Protocol/serial number

31775

Study information

Scientific 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

Acronym

MUK eleven

Study hypothesis

To main aim of this study is to determine the Maximum Tolerated Doses (MTDs) of REOLYSIN® in combination with lenalidomide or pomalidomide in two separate groups of patients with multiple myeloma demonstrating evidence of serological disease progression.

Ethics approval

Yorkshire & The Humber - Leeds West Research Ethics Committee, 09/11/2016, ref: 16/YH/0388

Study design

Non-randomised; Interventional; Design type: Treatment, Drug, Immunotherapy

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Haematological Oncology; UKCRC code/ Disease: Cancer/ Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue

Intervention

Participants will be treated with REOLYSIN® along with lenalidomide or pomalidomide, depending on which of these drugs they were
previously taking immediately before starting on the trial. Treatment will be given in cycles lasting 28 days in the following schedule:
Lenalidomide or pomalidomide - oral, on days 1-21
REOLYSIN® - intravenous infusion over 1 hour on days 1, 8, 15 and 22

Treatment will last until the participant’s multiple myeloma progresses, their doctor decides it is necessary to stop treatment or until the participant decides they do not want any more treatment within the study. The frequency of follow-up visits will be decided by the participant’s doctor but we will continue to collect data for up to 3 years.

Intervention type

Other

Phase

Phase I

Drug names

Primary outcome measures

Dose-limiting toxicities are measured in real-time for each patient to inform dose escalation decisions after cycle 1 (28 days) of treatment.

Secondary outcome measures

1. Safety profile of REOLYSIN® and lenalidomide or pomalidomide is assessed based on the occurrence of SAEs, SARs and SUSARs until 28 days after the last dose of trial treatment for each patient
2. Toxicity profile of REOLYSIN® and lenalidomide or pomalidomide is assessed based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre until 28 days after the last dose of trial treatment for each patient
3. Response rate (stable disease or better) is measured using IMWG criteria after 6 cycles of therapy in patients treated at the maximum tolerated dose
4. Maximum response within 6 cycles of therapy is measured using IMWG criteria in patients treated at the maximum tolerated dose
5. Maximum response overall is measured using IMWG criteria in patients treated at the maximum tolerated dose when they have finished their treatment.
6. Time to maximum response in patients treated at the maximum tolerated dose is measured using IMWG criteria when they have finished their treatment
7. Progression-free survival is calculated for each patient from the date of registration up to first documented evidence of disease progression or death. Measured only in patients treated at the maximum tolerated dose
8. Overall survival is calculated for each patient from the date of registration to death. Measured only in patients treated at the maximum tolerated dose.

Exploratory outcome measure:
Immune response biomarker profile of REOLYSIN® and lenalidomide or pomalidomide administered in combination.

Overall trial start date

30/06/2015

Overall trial end date

01/05/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Diagnosed with symptomatic multiple myeloma (according to IMWG 2014 criteria)
2. Evaluable disease by modified IMWG criteria (i.e. by abnormal serum M protein, urinary M protein or serum free light chain assays)
3. 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)
4. Life expectancy of ≥ 3 months
5. ECOG performance status of ≤2
6. Required laboratory values within 14 days prior to dose allocation:
7. Absolute neutrophil count ≥ 1.0 x109 /L. (growth factor support is not permitted)
8. Platelet count ≥ 70 x 109/L. (platelet support is not permitted; platelets < 70 but ≥ 25 acceptable if bone marrow is > 50% infiltrated by MM)
9. Haemoglobin ≥ 8 g/dL. Blood support is permitted
10. Serum bilirubin ≤ 2 x upper limit of normal (ULN)
11. ALT or AST ≤ 2.5 x ULN
12 Serum creatinine ≤ 2 x ULN
13. Corrected calcium ≤ 2.8 mmol/l
14. Negative HIV and viral (B and C) hepatitis test result within 14 days prior to dose allocation
15. Able to give informed consent and willing to follow trial protocol
16. Aged 18 years or over
17. All participants must agree to follow the Celgene Pregnancy Prevention Programme (PPP) and participate in the counselling associated with this:
18. 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
19. Females must agree to abstain from breastfeeding during trial participation and 28 days after trial drug discontinuation
20. 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
21. 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
22. 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 44; UK Sample Size: 44

Participant exclusion criteria

1. Non-secretory multiple myeloma
2. Pregnant (positive pregnancy test) in line with the Celgene Pregnancy Prevention Programme or breast feeding
3. 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
4. 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.
5. 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.
6. Any history of known hypersensitivity to any of the trial medications or excipients
7. Active symptomatic fungal, bacterial, and/or viral infection
8. 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
9. 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)
10. Radiotherapy or major surgery within 4 weeks prior to registration
11. Greater than or equal to grade 2 neuropathy, with or without pain

Recruitment start date

01/02/2017

Recruitment end date

01/11/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

University of Leeds

Sponsor details

Research and Development
34 Hyde Terrace
Leeds
LS2 9LN
United Kingdom
+44 113 392 6459
c.e.skinner@leeds.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Myeloma UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Plans to publish study results in a peer reviewed journal around one year after the end of the trial.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/05/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

15/09/2017: Internal review. 06/06/2017: Internal review.