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

Phase 1

• Conditions: Relapsed/refractory Hodgkin lymphoma; MedDRA version: 21.1Level: PTClassification code 10020266Term: Hodgkin's disease recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10020267Term: Hodgkin's disease refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002544-32-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-26
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Inclusion criteria for registration
•Age 16 or over
•Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in first relapse
•About to receive, receiving or within 14 days of first 2 cycles of first or second line salvage therapy (4 cycles if receiving treatment with brentuximab vedotin)
•Fit for autologous stem cell transplantation
•Written informed consent
•Willing to comply with the contraceptive requirements of the trial

Inclusion criteria – trial treatment
•Has received 2 cycles of first line or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)
•PET positive (Deauville score 4 or 5) after 2 cycles of first or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)
•Fit for further salvage chemotherapy
•ECOG performance status 0-1
•Creatinine clearance >30ml/min calculated by Cockroft-Gault formula
•Bilirubin <1.5 x ULN, ALT/AST <2.5 x ULN
•Adequate bone marrow function (Hb >80g/l, Platelets >50 x 10^9/l, neutrophils >1.0 x 10^9/l
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Exclusion criteria for registration
•Nodular lymphocyte predominant Hodgkin lymphoma
•Women who are pregnant or breastfeeding
•History of colitis, inflammatory bowel disease or pneumonitis
•Patients with autoimmune disorders excluding patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy
•Known history of hepatitis B or C infection
•Known HIV infection
•History of allergy (including severe/life threatening skin reaction) to monoclonal antibodies, anaphylaxis or uncontrolled allergy
•Major surgery within 4 weeks prior to registration
•Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months
•Non-haematological malignancy within the past 3 years (some exceptions apply – listed in trial protocol)

Exclusion criteria for trial treatment
•Deauville score 1-3 after 2 cycles of first or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)
•Positive serology for hepatitis B or C (unless due to vaccination)
•Active infection requiring systemic therapy
•Ongoing immunosuppressive therapy, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (=10mg prednisolone or equivalent per day).
•Chemo- or radiotherapy or corticosteroids at a dose of more than 10mg/day prednisolone or equivalent within 14 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.
•Treatment with any investigational agent within 28 days prior to planned start of nivolumab
•Ongoing grade 2-4 non-haematological toxicities related to prior Hodgkin lymphoma treatments, with the exception of alopecia and grade 2 fatigue
•Pregnant or breastfeeding women

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified