ANIMATE: Phase II Study of Nivolumab Monotherapy for Relapsed/Refractory Hodgkin Lymphoma

• Status: Recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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 2 cycles of first or second line salvage therapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Nivolumab

Criteria

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 within 14 days of receiving first 2 cycles of first or second line salvage therapy (4 cycles if receiving treatment with brentuximab vedotin)

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, (4 cycles if receiving treatment with brentuximab vedotin)

2. PET positive (Deauville score 4 or 5) after 2 cycles of first or second line salvage chemotherapy (4 cycles if receiving treatment with brentuximab vedotin)

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 2 cycles of first or second line salvage chemotherapy (4 cycles if receiving treatment with brentuximab vedotin)

2. Positive serology for hepatitis B or C (unless due to vaccination)

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. Chemo- or radiotherapy or corticosteroids at a dose of more than 10mg per 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.

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