A Phase II Study of Nivolumab Monotherapy in Patients With Relapsed/Refractory Hodgkin Lymphoma Fit for Autologous Stem Cell Transplant Who Fail to Reach Complete Metabolic Remission After First or Second Line Salvage Therapy

UCL/15/0515

This is a single-arm, phase II, multi-centre study of the safety and efficacy of the PD-1 inhibitor, nivolumab, as second-line or third-line salvage therapy as a bridge to stem cell transplant (SCT) in relapsed/ refractory classical Hodgkin lymphoma patients not achieving a complete metabolic response (CMR) on FDG-PET-CT scan after first or second line salvage therapy.

2018-12-03

2023-03-01

2026-02-28

Active (not recruiting)

Early phase I

78

Inclusion criteria for study registration: 1. Age 16 or over 2. Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in first relapse 3. About to receive or receiving first or second line salvage therapy (up to a maximum of 14 days after last treatment) 4. Fit for autologous stem cell transplantation 5. Written informed consent 6. Willing to comply with the contraceptive requirements of the trial Exclusion criteria for study registration: 1. Nodular lymphocyte predominant Hodgkin lymphoma 2. Women who are pregnant or breastfeeding 3. History of colitis, inflammatory bowel disease or pneumonitis 4. Patients with autoimmune disorders, except patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy 5. Known history of hepatitis B or C infection 6. Known HIV infection 7. History of allergy (including severe/life threatening skin reaction) to monoclonal antibodies, anaphylaxis or uncontrolled allergy 8. Major surgery within 4 weeks prior to registration 9. Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months 10. Non-haematological malignancy within the past 3 years (with some exceptions - listed in protocol) Inclusion criteria for trial treatment: 1. Has received 2 cycles of first or second line salvage chemotherapy 2. PET positive (Deauville score 4 or 5) after first or second line salvage chemotherapy 3. Fit for further salvage chemotherapy 4. ECOG performance status 0-1 5. Creatinine clearance \>30ml/min calculated by Cockcroft-Gault formula 6. Bilirubin \<1.5 x ULN, ALT/AST \<2.5 x ULN 7. Adequate bone marrow function (Hb \>80g/l, Platelets \>50 x 10\^9/l, neutrophils \>1.0 x 10\^9/l) Exclusion criteria for trial treatment: 1. Deauville score 1-3 after first or second line salvage chemotherapy 2. Positive serology for hepatitis B or C (some exclusions apply - see protocol) 3. Active infection requiring systemic therapy 4. Ongoing requirement for immunosuppressive therapy, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone per day, or the equivalent) 5. Corticosteroids at a dose of more than 10mg per day prednisolone or equivalent within 7 days prior to response PET-CT. NOTE: corticosteroids can be used AFTER a positive PET-CT scan for symptomatic disease but must be weaned to a dose of prednisolone ≤10mg/day or less (or equivalent) at least 7 days prior to starting nivolumab. 6. Treatment with any investigational agent within 28 days prior to planned start of nivolumab 7. Ongoing grade 2-4 non-haematological toxicities related to prior Hodgkin lymphoma treatments, with the exception of alopecia and grade 2 fatigue 8. Pregnant or breastfeeding women

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'This is a single-arm, phase II, multi-centre study. It will use an Ahern single stage design with independent trials steering committee review to monitor for safety and efficacy.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 78, 'type': 'ACTUAL'}}

2024-05-10