Pembrolizumab plus chemotherapy for diffuse large B-cell lymphoma that has come back or does not respond to treatment

Phase 2

• Conditions: Relapsed/refractory diffuse large B-cell lymphoma; Cancer; Diffuse large B-cell lymphoma

• Registration Number: ISRCTN86607306
• Lead Sponsor: niversity Hospital Southampton NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-05-11
• Last Update Posted: 28 August 2023
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

1. Histologically proven CD20 +ve diffuse large B-cell lymphoma, preferably with sufficient diagnostic material,obtained either at diagnosis or relapse (the latter is preferable) that is available to forward to the Haematological Malignancies Diagnostic Service (HMDS)
2. Refractory to, or relapsed following, first-line or second-line treatments with rituximab concurrently with anthracycline or anthracenedione-based chemotherapy or similar (etoposide allowed if comorbid). Refractory disease must fulfil one of the following:
2.1. Continuing partial response (PR) from termination of first-line treatment. It is strongly recommended the lymphoma be reconfirmed by biopsy, however, if these procedures are deemed to be inappropriate, the CI may determine eligibility following review of the imaging results and disease history.
2.2. Continuing stable disease (SD) from termination of first-line treatment. Reconfirmation of the lymphoma by biopsy (preferred) is recommended but not mandatory
2.3. Progressive disease (PD). Biopsy or reconfirmation of the lymphoma is recommended but not mandatory
3. Potentially eligible for high-dose therapy and peripheral blood progenitor cell rescue in the event of response
4. Positive lesions shown on baseline PET-CT must be compatible with CT defined anatomical tumour sites
5. At least two demarcated lesions/nodes with a long axis >1.5 cm and a short axis equal to 1.0 cm or one clearly demarcated lesion/node with a long axis >2.0 cm and short axis of 1.0 cm
6. Previous therapy related toxicity should have resolved to a grade that the investigator deems appropriate to commence further treatment
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 – 1
8. Has provided written informed consent
9. Willing to use acceptable contraception (see Section 4.6)
10. Aged 18 years or over

Exclusion Criteria

1. Previous lymphoma cancer treatment beyond third line
2. Radiotherapy or cytotoxic drugs within two weeks of trial treatment
3. Major surgery within 4 weeks of trial registration. If a subject had major surgery,more than 4 weeks ago, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
4. Treatment with any unlicensed drug within 4 weeks of trial treatment
5. History of stroke or intracranial haemorrhage within 6 months prior to registration
6. Pre-existing peripheral neuropathy grade >2
7. Clinically significant cardiac disease (inc. unstable angina,acute myocardial infarction,congestive heart failure,a current LVEF of <40%) within 6 months of registration
8. Any significant uncontrolled medical condition or known hypersensitivity to the study drugs
9. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as,but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis
10. Other past or current malignancy within 2 years prior to registration unless in the opinion of the investigator it does not contraindicate participation in the study. Subjects who have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
11. Known CNS involvement
12. Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care,prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.
13. Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible
14. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible
15. Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible
16. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
17. Screening laboratory values :
17.1. platelets <75 x 10e9/L (unless due to lymphoma involvement of the bone marrow)
17.2. neutrophils <1.0 x 10e9/L (unless due to lymphoma involvement of the bone marrow)
17.3. creatinine >2.0 times upper normal limit (unless due to lymphoma or unless creatinine clearance >50 ml/min)
17.4. total bilirubin >1.5 times upper normal limit (unless due to lymphoma or a known history of Gilbert’s disease)
17.5. ALT/AST >2.5 times upper normal limit (unless due to lymphoma)
17.6. Alkaline phosphatase >2.5 times upper normal limit (unless due to lymphoma)
18. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. (Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone will be eligible as will be patients with controlled Type I diabetes mellitus on a stable dose of insulin).
19. Patients who have previously undergone allogeneic transplantation
20. Live vaccination within 28 days of study treatment
21. Pregnant or lactating females. Women of child-bearing potential should have negative pregnancy tes

Study & Design

• Study Type: Interventional
• Study Design: Not specified