- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03630042
Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia (PembroWM)
A Phase II Trial to Investigate the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia
This study is for patients who have previously been treated for Waldenström's macroglobulinaemia (WM) and their disease has either not responded (known as refractory disease) or has returned (known as relapsed disease). Through this study, the researchers would like to find out whether treating these patients with drugs called rituximab and pembrolizumab is a safe and effective combination for this disease.
In this study, pembrolizumab and rituximab will be given together. In other studies pembrolizumab has been shown to be effective at treating diseases similar to WM. The researchers want to test whether giving pembrolizumab and rituximab together is safe and effective.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: PembroWM Trial Coordinator
- Phone Number: 02076799860
- Email: ctc.PembroWM@ucl.ac.uk
Study Locations
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Bristol, United Kingdom, BS1 3NU
- Bristol Haematology & Oncology Medical Centre, University Hospitals Bristol and Weston NHS Foundation Trust
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Norwich, United Kingdom, NR4 7UY
- Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust
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Devon
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Plymouth, Devon, United Kingdom, PL6 8DH
- Derriford Hospital, Univeristy Hospitals Plymouth NHS Trust
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Torquay, Devon, United Kingdom, TQ2 7AA
- Torbay and South Devon NHS Foundation Trust
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Dorset
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Bournemouth, Dorset, United Kingdom, BH7 7DW
- Royal Bournemouth Hospital, University Hospitals Dorset NHS Foundation Trust
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Greater London
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London, Greater London, United Kingdom, EC1A 7BE
- St Bartholomew's Hospital, Barts Health NHS Trust
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London, Greater London, United Kingdom, NW1 2PG
- UCLH, Univeristy College London Hospitals NHS Foundation Trust
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Greater Manchester
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Manchester, Greater Manchester, United Kingdom, M20 4BX
- The Christie Hospital, The Christie NHS Foundation Trust
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Oxfordshire
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Oxford, Oxfordshire, United Kingdom, OX3 7LE
- Churchill Hospital, Oxford Univeristy NHS Foundation Trust
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion criteria
- Patients ≥18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Presence of measurable disease, (defined as a serum IgM level of >0.5g/L) and fulfils other World Health Organisation (WHO) diagnostic criteria for WM
- Relapsed or refractory WM who have received ≥1 prior lines of therapy
- Adequate renal function: estimated creatinine clearance ≥ 30ml/min as calculated using the Cockroft-Gault equation
Adequate liver function, including:
- Bilirubin ≤1.5x the upper limit of normal (ULN)
- Aspartate or alanine transferase (AST or ALT) ≤2.5 x ULN
Adequate organ and bone marrow function:
- Neutrophils ≥0.75x109/L
- Platelets ≥50x109/L
- Willing to comply with the contraceptive requirements of the trial
- Negative serum or highly sensitive urine pregnancy test for women of childbearing potential (WOCBP)
- Written informed consent
Exclusion criteria
- Refractory to rituximab as defined by progression on/within 6 months of finishing a rituximab based regimen
- Women who are pregnant or breastfeeding, or males expecting to conceive or father children at any point from the start of treatment until 4 months after the last administration of pembrolizumab
- Clinically significant cardiac disease within 6 months prior to registration including unstable angina or myocardial infarction, uncontrolled congestive heart failure (NYHA class III-IV), and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.
- History of significant cerebrovascular disease in last 6 months
- Known central nervous system involvement of WM
- Clinically significant active infection requiring antibiotic or antiretroviral therapy (including Hepatitis B, C or human immunodeficiency virus (HIV))
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
Active autoimmune disease apart from:
- Type I diabetes or thyroid disease, controlled on medication
- Skin conditions such as psoriasis, vitiligo or alopecia not requiring systemic treatment
- Auto-immune thrombocytopenia, thought to be secondary to WM, provided that platelet count meet the criteria specified above, on daily doses of corticosteroid ≤10mg prednisolone or equivalent
- Prior history of haemolytic anaemia (either warm or cold)
- History of colitis
- History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Systemic anti-cancer therapy within 4 weeks prior to trial registration (except for BTK inhibitors, which may continue until cycle 1, day 1 of trial treatment)
- Received a T cell depleting antibody (e.g. Campath) within 3 months prior to starting treatment
- Received a live vaccine within 30 days prior to starting treatment
- Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis
- Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to starting treatment (unless prior agreed with the TMG)
- Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
- Positive serology for Hepatitis B defined as a positive test for HepB surface antigen (HBsAg). Note: patients who are HepB core antibody (HBcAb) positive will only be eligible for the study if the HepB virus deoxyribonucleic acid (HBV DNA) test is negative and patients are willing to undergo monthly monitoring for HBV reactivation
- Major surgery within 4 weeks prior to trial registration
- Prior therapy with an anti-PD-1,anti-PD-L1 or CTLA4 monoclonal antibody
- Prior allogeneic bone marrow transplantation
- Diagnosis of prior immunodeficiency or organ-transplant requiring immunosuppressive therapy or known HIV or acquired immunodeficiency syndrome (AIDS)-related illness
- Current or prior use of immunosuppressive therapy within 7 days prior to start of treatment except the following: intranasal, inhaled, topical steroids or local steroid injections (eg. Intra-articular injections); systemic corticosteroids at physiologic doses (<10mg/ day of prednisolone or equivalent)
- Known or suspected hypersensitivity to components of pembrolizumab and/or rituximab (or other CD20 monoclonal antibody)
- Current participation in any other clinical trial of an investigational medicinal product (CTIMP)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Pembrolizumab and Rituximab
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200 mg IV dose given on day 1 of a three week cycle
375 mg/m2 IV dose given up to 8 times in the trial
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients achieving at least a major response rate at 24 weeks post commencing treatment
Time Frame: 24 weeks
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defined as greater than 50% reduction in paraprotein
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24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of pembrolizumab and rituximab as assessed by the frequency of serious and non-serious adverse events, according to CTCAE v5.0
Time Frame: until 5 months post last IMP administration
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As assessed by the number and grade of serious and non-serious adverse events, graded according to CTCAE v5.0
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until 5 months post last IMP administration
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Complete response rate at 24 weeks post commencing treatment
Time Frame: 24 weeks
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24 weeks
|
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Very good partial response rate at 24 weeks post commencing treatment
Time Frame: 24 weeks
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24 weeks
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Time to maximal response as determined by the time of registration to the maximal disease response
Time Frame: Assessed at 12 weeks, 24 weeks and 1 year after commencing treatment
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Assessed at 12 weeks, 24 weeks and 1 year after commencing treatment
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Time to next treatment
Time Frame: Assessed once per year after completing treatment (average of 1 year)
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as determined by the time from registration to the next line of therapy
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Assessed once per year after completing treatment (average of 1 year)
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Progression free survival (PFS) at 1 and 2 years
Time Frame: 1 and 2 years post commencing treatment
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1 and 2 years post commencing treatment
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Overall survival (OS) at 1 and 2 years
Time Frame: 1 and 2 years post commencing treatment
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1 and 2 years post commencing treatment
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Quality of Life - Change in quality of life (QoL) at 24 weeks post commencing treatment as assessed by EORTC QLQ-C30 questionnaire
Time Frame: 24 weeks
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Change in quality of life (QoL) at 24 weeks post commencing treatment as assessed by EORTC QLQ-C30 questionnaire.
Daily activities and thoughts/feelings experienced by the patient over the week preceding questionnaire completion are graded on a scale from '1-not at all' to '4-very much'.
Also rating of overall health and quality of life from '1-very poor' to '7-excellent'
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24 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jaimal Kothari, Oxford University Hospitals NHS Trust
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Waldenstrom Macroglobulinemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
- Rituximab
Other Study ID Numbers
- UCL/18/0131
- 2018-001767-23 (EudraCT Number)
- MISP # 56775 (Other Grant/Funding Number: Merck, Sharp & Dohme Ltd)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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