Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia

NCT03630042 | Completed Phase 2 Results DMC

• 3 other identifiers: UCL/18/01312018-001767-23MISP # 56775
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 9

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.

Conditions

Waldenstrom Macroglobulinemia

Keywords

Waldenstrom Macroglobulinemia; Relapsed; Refractory; Rituximab; Pembrolizumab

Outcome Measures

Primary Outcomes (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.

  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

  until 5 months post last IMP administration

• Complete Response Rate at 24 Weeks Post Commencing Treatment

  24 weeks

• Very Good Partial Response Rate at 24 Weeks Post Commencing Treatment

  24 weeks

• Time to Maximal Response as Determined by the Time of Registration to the Maximal Disease Response

  Assessed at 12 weeks, 24 weeks and 1 year after commencing treatment

• Time to Next Treatment

  Assessed once per year after completing treatment (average of 1 year)

Study Arms (1)

Pembrolizumab and Rituximab

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Rituximab

Interventions

Pembrolizumab DRUG

200 mg IV dose given on day 1 of a three week cycle

Pembrolizumab and Rituximab

Rituximab DRUG

375 mg/m2 IV dose given up to 8 times in the trial

Pembrolizumab and Rituximab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University College, London: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (9)

Derriford Hospital, Univeristy Hospitals Plymouth NHS Trust

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Torbay and South Devon NHS Foundation Trust

Torquay, Devon, TQ2 7AA, United Kingdom

Location

Royal Bournemouth Hospital, University Hospitals Dorset NHS Foundation Trust

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

St Bartholomew's Hospital, Barts Health NHS Trust

London, Greater London, EC1A 7BE, United Kingdom

Location

UCLH, Univeristy College London Hospitals NHS Foundation Trust

London, Greater London, NW1 2PG, United Kingdom

Location

The Christie Hospital, The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital, Oxford Univeristy NHS Foundation Trust

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Bristol Haematology & Oncology Medical Centre, University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS1 3NU, United Kingdom

Location

Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, NR4 7UY, United Kingdom

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Recurrence

Interventions

pembrolizumab; Rituximab

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; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The sample size of 42 was not reached so limited conclusions can be made.

Results Point of Contact

• Title: Jaimal Kothari
• Organization: Oxford University Hospital NHS Trust

Jaimal.Kothari@ouh.nhs.uk

NA

Study Officials

• Jaimal Kothari

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single arm, non randomised phase II trial

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 14, 2018
• Study Start: September 6, 2019
• Primary Completion: September 21, 2021
• Study Completion: February 14, 2024
• Last Updated: November 7, 2024
• Results First Posted: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (9)