Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma

NCT03015922 | Unknown Phase 1 DMC

• 1 other identifier: HM16/118
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities

  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.

  After cycle 1 (28 days) of treatment. Assessed in real-time for each patient to inform dose escalation decisions.

Secondary Outcomes (10)

• Safety profile of REOLYSIN® and lenalidomide

  Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.

• Safety profile of REOLYSIN® and pomalidomide

  Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.

• Toxicity profile of REOLYSIN® and lenalidomide

  Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.

• Toxicity profile of REOLYSIN® and pomalidomide

  Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.

• Response rate (stable disease or better) after 6 cycles of therapy

  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.

Other Outcomes (2)

• Immune response biomarker profile of REOLYSIN and lenalidomide administered in combination

  This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.

• Immune response biomarker profile of REOLYSIN® and pomalidomide administered in combination

  This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.

Study Arms (1)

Lenalidomide or pomalidomide, plus REOLYSIN

EXPERIMENTAL

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; Biological: REOLYSIN

Interventions

Lenalidomide or Pomalidomide DRUG

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).

Lenalidomide or pomalidomide, plus REOLYSIN

REOLYSIN BIOLOGICAL

Patients will receive Reolysin alongside either lenalidomide or pomalidomide

Also known as: Pelareorep, Reovirus

Lenalidomide or pomalidomide, plus REOLYSIN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Leeds: lead
• Myeloma UK: collaborator
• Oncolytics Biotech: collaborator
• Celgene Corporation: collaborator

Study Sites (2)

St James's University Hospital

Leeds, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; pomalidomide; reolysin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gordon Cook

  St. James's University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Haematologist

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: January 10, 2017
• Study Start: June 5, 2017
• Primary Completion: September 1, 2021
• Study Completion: October 1, 2021
• Last Updated: January 22, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)