Brief Title
Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia
Official Title
A Phase II Trial to Investigate the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia
Brief 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). 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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Percentage of patients achieving at least a major response rate at 24 weeks post commencing treatment
Secondary Outcome
Safety and tolerability of pembrolizumab and rituximab as assessed by the frequency of serious and non-serious adverse events, according to CTCAE v5.0
Condition
Waldenstrom Macroglobulinemia
Intervention
Pembrolizumab
Study Arms / Comparison Groups
Pembrolizumab and Rituximab
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
42
Start Date
September 6, 2019
Completion Date
December 2023
Primary Completion Date
December 31, 2021
Eligibility Criteria
Inclusion criteria
1. Patients ≥18 years old
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
3. 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
4. Relapsed or refractory WM who have received ≥1 prior lines of therapy
5. Adequate renal function: estimated creatinine clearance ≥ 30ml/min as calculated using
the Cockroft-Gault equation
6. Adequate liver function, including:
- Bilirubin ≤1.5x the upper limit of normal (ULN)
- Aspartate or alanine transferase (AST or ALT) ≤2.5 x ULN
7. Adequate organ and bone marrow function:
- Neutrophils ≥0.75x109/L
- Platelets ≥50x109/L
8. Willing to comply with the contraceptive requirements of the trial
9. Negative serum or highly sensitive urine pregnancy test for women of childbearing
potential (WOCBP)
10. Written informed consent
Exclusion criteria
1. Refractory to rituximab as defined by progression on/within 6 months of finishing a
rituximab based regimen
2. 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
3. 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.
4. History of significant cerebrovascular disease in last 6 months
5. Known central nervous system involvement of WM
6. Clinically significant active infection requiring antibiotic or antiretroviral therapy
(including Hepatitis B, C or human immunodeficiency virus (HIV))
7. Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological,
cerebral or psychiatric disease
8. 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
9. 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
10. Prior history of haemolytic anaemia (either warm or cold)
11. History of colitis
12. History of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
13. 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)
14. Received a T cell depleting antibody (e.g. Campath) within 3 months prior to starting
treatment
15. Received a live vaccine within 30 days prior to starting treatment
16. 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
17. 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)
18. Patients known or suspected of not being able to comply with a study protocol (e.g.
due to alcoholism, drug dependency or psychological disorder)
19. 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
20. Major surgery within 4 weeks prior to trial registration
21. Prior therapy with an anti-PD-1,anti-PD-L1 or CTLA4 monoclonal antibody
22. Prior allogeneic bone marrow transplantation
23. Diagnosis of prior immunodeficiency or organ-transplant requiring immunosuppressive
therapy or known HIV or acquired immunodeficiency syndrome (AIDS)-related illness
24. 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)
25. Known or suspected hypersensitivity to components of pembrolizumab and/or rituximab
(or other CD20 monoclonal antibody)
26. Current participation in any other clinical trial of an investigational medicinal
product (CTIMP)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jaimal Kothari, 02076799860, [email protected]
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT03630042
Organization ID
UCL/18/0131
Secondary IDs
2018-001767-23
Responsible Party
Sponsor
Study Sponsor
University College, London
Collaborators
Merck Sharp & Dohme LLC
Study Sponsor
Jaimal Kothari, Principal Investigator, Oxford University Hospitals NHS Trust
Verification Date
May 2021