Waldenstrom MacroglobulinemiaPhase 2PembroWMNCT03630042
Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia
A Phase 2 study testing Pembrolizumab and Rituximab in people with Waldenstrom Macroglobulinemia, run by University College, London at 9 sites in United Kingdom.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom Macroglobulinemia
- What is being tested?
- Pembrolizumab and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- 6 Sep 2019to 14 Feb 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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))
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- 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)
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United Kingdom9 sites
Royal Bournemouth Hospital, University Hospitals Dorset NHS Foundation Trust
Bournemouth, Dorset, BH7 7DW
Bristol Haematology & Oncology Medical Centre, University Hospitals Bristol and Weston NHS Foundation Trust
Bristol, BS1 3NU
St Bartholomew's Hospital, Barts Health NHS Trust
London, Greater London, EC1A 7BE
UCLH, Univeristy College London Hospitals NHS Foundation Trust
London, Greater London, NW1 2PG
The Christie Hospital, The Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX
Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, NR4 7UY
Churchill Hospital, Oxford Univeristy NHS Foundation Trust
Oxford, Oxfordshire, OX3 7LE
Derriford Hospital, Univeristy Hospitals Plymouth NHS Trust
Plymouth, Devon, PL6 8DH
Torbay and South Devon NHS Foundation Trust
Torquay, Devon, TQ2 7AA
About this study
Official title: 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.
- Conditions
- Waldenstrom Macroglobulinemia
- Being tested
- Pembrolizumab, Rituximab
- Keywords
- Waldenstrom Macroglobulinemia, Relapsed, Refractory, Rituximab, Pembrolizumab
- Medical subject headings
- Waldenstrom Macroglobulinemia, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
200 mg IV dose given on day 1 of a three week cycle
RituximabDrug
375 mg/m2 IV dose given up to 8 times in the trial
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab and Rituximab | Experimental | Not described Receives: Drug: Pembrolizumab; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Achieving at Least a Major Response Rate at 24 Weeks Post Commencing Treatment
The primary outcome is the percentage of patients achieving at least a major response rate at 24 weeks post commencing treatment. A major response rate is defined as a greater than 50% reduction in paraprotein measurement - this is in line with international recognised response criteria for the disease under investigation. In this single arm study all patients receiving treatment were considered applicable for endpoint analysis. There is no comparison as there is only one arm.
Measured: 24 weeks
Secondary outcomes (8)
Safety and Tolerability of Pembrolizumab and Rituximab as Assessed by the Frequency of Serious and Non-serious Adverse Events, According to CTCAE v5.0
As assessed by the number and grade of serious and non-serious adverse events, graded according to CTCAE v5.0
Measured: until 5 months post last IMP administration
Complete Response Rate at 24 Weeks Post Commencing Treatment
Measured: 24 weeks
Very Good Partial Response Rate at 24 Weeks Post Commencing Treatment
Measured: 24 weeks
Time to Maximal Response as Determined by the Time of Registration to the Maximal Disease Response
Measured: Assessed at 12 weeks, 24 weeks and 1 year after commencing treatment
Time to Next Treatment
as determined by the time from registration to the next line of therapy
Measured: Assessed once per year after completing treatment (average of 1 year)
Progression Free Survival (PFS) at 1 and 2 Years
Measured: 1 and 2 years post commencing treatment
Overall Survival (OS) at 1 and 2 Years
Measured: 1 and 2 years post commencing treatment
Quality of Life - Change in Quality of Life (QoL) at 24 Weeks Post Commencing Treatment as Assessed by EORTC QLQ-C30 Questionnaire
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'
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start6 Sep 2019
- Primary completion21 Sep 2021
- Study completion14 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Waldenstrom MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A single arm, non randomised phase II trial
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Jaimal Kothari, Principal investigator, Oxford University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03630042
- Sponsor's protocol ID
- UCL/18/0131
- Other IDs
- 2018-001767-23, MISP # 56775, 2018
- Acronym
- PembroWM
- Status last verified
- Nov 2024
- First submitted
- 13 Jul 2018
- Last updated
- 7 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No