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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Other trials in United Kingdom

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.

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 groups in NCT03630042
Study groupRoleWhat they receive
Pembrolizumab and RituximabExperimentalNot described
Receives: Drug: Pembrolizumab; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

  1. 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

  2. Complete Response Rate at 24 Weeks Post Commencing Treatment

    Measured: 24 weeks

  3. Very Good Partial Response Rate at 24 Weeks Post Commencing Treatment

    Measured: 24 weeks

  4. 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

  5. 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)

  6. Progression Free Survival (PFS) at 1 and 2 Years

    Measured: 1 and 2 years post commencing treatment

  7. Overall Survival (OS) at 1 and 2 Years

    Measured: 1 and 2 years post commencing treatment

  8. 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.

  1. First posted14 Aug 2018
  2. Study start6 Sep 2019
  3. Primary completion21 Sep 2021
  4. Study completion14 Feb 2024

Resources

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)
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
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Rituximab in people with Waldenstrom Macroglobulinemia, run by University College, London at 9 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Patients Achieving at Least a Major Response Rate at 24 Weeks Post Commencing Treatment (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03630042.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.

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