MUK eleven
Research type
Research Study
Full 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
IRAS ID
209046
Contact name
Gordon Cook
Contact email
Sponsor organisation
University of Leeds
Eudract number
2016-001564-11
Clinicaltrials.gov Identifier
RV-CL-MM-PI-005489, Celgene reference
Duration of Study in the UK
2 years, 8 months, 31 days
Research summary
Summary of Research
Multiple myeloma (MM) is a cancer of the bone marrow with an incidence of approximately 5500 new cases per year. Despite the availability of a range of treatments, most MM patients will relapse and eventually become resistant to current therapies.
REOLYSIN® is a type of virus (reovirus) which attacks cancer cells, but not normal cells, and also activates the body’s immune system. Most people have contact with reovirus in the environment but it doesn’t usually cause any symptoms or illness. Previous trials of REOLYSIN® in both solid and haematological cancers have shown that it is well-tolerated with manageable side effects and indicate that it may be an effective treatment.
Lenalidomide and pomalidomide are immunomodulatory drugs (IMiDs) which act against MM cells in a range of ways, including affecting the immune system. Patients who develop relapsed MM while receiving IMiDs have a competent immune system and it is thought that the addition of REOLYSIN® at this point may stimulate immune-mediated disease control. The proposed study will recruit patients (up to 44 in total) currently receiving either lenalidomide or pomalidomide whose disease is relapsing. The aim of this trial is to determine the maximum tolerated dose (MTD) of REOLYSIN® that can be given in combination with lenalidomide or pomalidomide. The trial will also investigate the safety, side effects and effectiveness of this treatment combination.
Participants will be recruited from NHS Hospitals throughout the UK, which are approved research sites within the Myeloma UK Early Phase Clinical Network. Participants will be required to attend hospital regularly for tests and they will receive REOLYSIN® treatment, which is given by drip into a vein, once a week. Lenalidomide and pomalidomide are given orally. Participants will receive the trial treatment until their disease progresses further or if the treatment causes unacceptable side effects.Summary of Results
Abbreviation list:
CTCAE – Common terminology for adverse events DLT – Dose Limiting Toxicity ECG – Electrocardiogram ECOG – Eastern Cooperative Oncology Group IMWG - International Myeloma Working Group ISS - International Staging System MedDRA – Medical dictionary for Regulatory Activities SAE – Serious adverse event SAR – Serious adverse reaction SUSAR – Suspected unexpected serious adverse reaction
TCID50 – Median Tissue Culture Infection DoseParticipant flow:
Four patients were consented and registered to the study. Patient 4 was found to be ineligible due to lack of evidence of disease progression and so did not go on to receive treatment. All three remaining patients were allocated to receive Lenalidomide. Patients 1 and 2, the first cohort of 2, were allocated to dose level 1 (Reolysin® 1x1010 TCID50 and Lenalidomide 10mg or the maximum previously tolerated dose if lower), and as neither experienced a DLT, the dose level was increased to dose level 2 (Reolysin® 1x1010 TCID50 and Lenalidomide maximum previously tolerated dose) for patient 3. Only patient 1 attended off treatment follow-ups at 6- and 12- weeks post end of treatment.Baseline characteristics:
All three treated patients were male and between the ages of 58-71 at the time of registration. At baseline, two patients had an ECOG performance status of 0, and one patient had a status of 1. All three patients had stage I multiple myeloma as classified by the ISS at baseline. Two patients had a normal ECG baseline result, and one was abnormal.Outcome measures:
As the MUK eleven trial closed early with only a small number of participants, a full final analysis was not undertaken, and data are instead presented as summaries in the subsections below.DLTs:
All three patients were evaluable for DLTs, but no DLTs were reported during the DLT reporting period.Treatment received and reasons for stopping treatment:
Two patients commenced two cycles of treatment, and one patient commenced all six cycles of treatment. Treatment discontinuation was due to an adverse event for one patient, and due to disease progression for the other two patients. There were no withdrawals.Response to treatment and timing of assessment (from baseline):
Response assessments were carried out on day 1 of each of the 6 cycles, at the end of treatment and, if applicable, at off-treatment follow-ups. The best response recorded was ‘stable disease or no change’. All 3 patients progressed, at between 47- and 153- days post-trial registration. Disease progression is defined as serological or clinical evidence of progression compared to baseline assessment, according to the IMWG criteria. No deaths were reported.SAEs, SARs, SUSARs and adverse events:
One SAE occurred (CTCAE: Grade 2 Pyrexia, MedDRA: Immune system disorder) which was classified as expected for Reolysin and Lenalidomide, definitely related to Reolysin and unlikely to be related to Lenalidomide. The patient recovered from this SAE. No SUSARs were reported.
All reported adverse events recorded are summarised below:
Neutropenia was reported at CTCAE grades 2, 3 and 4.
Atelectasis, Back pain, Dizziness, Headache, Hypocalcaemia, Hypokalaemia and Vomiting were reported at CTCAE grade 1.
Fever, flu like symptoms, nausea and hypophosphatemia were reported at CTCAE grade 2.REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
16/YH/0388
Date of REC Opinion
9 Nov 2016
REC opinion
Further Information Favourable Opinion