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

Hodgkin Lymphoma Clinical Trial

— ANIMATE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03337919
• Other study ID #: UCL/15/0515
• Secondary ID: CA-209-4452017-0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 3, 2018
• Est. completion date: February 28, 2026

Study information

• Verified date: May 2024
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 first or second line salvage therapy.

Description:

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

Approximately 120 patients with relapsed/refractory classical Hodgkin lymphoma will be registered while undergoing first or second line salvage therapy (first line is preferred).

Patients will have a centrally reviewed PET CT scan after first or second line salvage therapy. Those with complete metabolic response (CMR) on PET CT scan (Deauville score 1-3) will not be eligible for trial treatment. They will be followed up for trial data collection purposes, and further management will be at their treating clinician's discretion.

Patients achieving less than CMR on central review of FDG-PET (Deauville score 4-5) will be eligible to receive up to 8 x 2-weekly nivolumab infusions. 30 patients will be treated on the trial.

After 4 courses of nivolumab, patients will have an additional centrally reviewed PET-CT scan (PET4). Patients achieving CMR will stop trial treatment, and enter follow up. Further treatment will be at their clinician's discretion but is likely to be stem cell transplant (SCT). Patients with partial metabolic response (PMR) or stable disease (SD) on PET4 will receive a further 4 cycles of nivolumab, again followed by a centrally reviewed PET-CT scan (PET8) to assess final response.

Further management after PET8 will be at the discretion of the treating clinician, although it is anticipated that those with CMR or PMR will proceed to SCT. If PET8 shows less than CMR (i.e. PMR or SD), patients who consent will have a further biopsy to exclude false positive PET signal; this will be centrally reviewed.

Patients with progressive metabolic disease (PMD) on nivolumab at any point will stop trial treatment. If a repeat biopsy is obtained to confirm progressive disease histologically, the biopsy material will be centrally reviewed.

Patients will be followed up for a minimum of 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 78
• Est. completion date: February 28, 2026
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Nivolumab
Up to 8 cycles of nivolumab

Locations

Country	Name	City	State
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Guy's Hospital	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Norfolk & Norwich University Hospital	Norwich	Norfolk
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Bristol-Myers Squibb

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biopsy-negative PMR rate	Correlation of PET positive disease with histological evidence of disease on post-treatment repeat biopsy to establish biopsy negative PMR rate (subject to patient consent)	4 months
Other	Serological biomarkers of response to nivolumab	Correlation of disease response with serological markers such as serum Thymus and activation-regulated chemokine (TARC) levels	5 months
Other	Immunological biomarkers of response to treatment	Evaluate the correlation between response to nivolumab and biological parameters e.g. PD-L1 expression on Reed Sternberg cells	4 months
Primary	Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab	Rate of patients achieving complete metabolic response (CMR) on PET-CT scan following 4 or 8 cycles of nivolumab	4 months
Secondary	Progression-free survival	Progression-free survival at 1 year; also to be analysed stratified by partial metabolic response vs complete metabolic response.	1 year
Secondary	Overall survival	Overall survival at 1 year; also to be analysed stratified by partial metabolic response (PMR) vs complete metabolic response (CMR).	1 year
Secondary	Proportion of patients progressing to stem cell transplant	Proportion of patients progressing to autologous or allogeneic stem cell transplant	1 year
Secondary	Adverse events [Safety and toxicity of nivolumab]	Adverse events and serious adverse events occurring in patients treated with nivolumab, in particular autoimmune toxicity	3 years
Secondary	Transplant-related mortality	Proportion of patients treated with nivolumab that subsequently die of transplant-related causes	3 years
Secondary	Transplant-related morbidity	Proportion of patients treated with nivolumab that go on to suffer serious complications of allogeneic transplant (grade 3-4 graft-versus-host disease, hyperacute graft-versus-host disease and steroid-responsive febrile syndrome)	3 years

External Links

•   CR UK & UCL Cancer Trials Centre