Clinical Trials /

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

NCT03337919

Description:

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.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ANIMATE: Phase II Study of Nivolumab Monotherapy for Relapsed/Refractory Hodgkin Lymphoma
  • 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 IDs

  • ORG STUDY ID: UCL/15/0515
  • SECONDARY ID: CA-209-445
  • NCT ID: NCT03337919

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
NivolumabOpdivo®Nivolumab

Purpose

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.

Detailed 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 2 cycles of
      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 2 cycles of the salvage therapy
      they are receiving (or 4 cycles if they are undergoing treatment with brentuximab vedotin).
      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.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalUp to 8 x 2-weekly cycles of nivolumab 240mg IV. Interim PET-CT scan to be performed after 4 cycles, and centrally reviewed. Patients will stop treatment after 4 cycles if they have complete metabolic response or progressive metabolic disease. If they have partial metabolic response or stable disease, they will continue to 8 cycles.
  • Nivolumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab
Time Frame:4 months
Safety Issue:
Description:Rate of patients achieving complete metabolic response (CMR) on PET-CT scan following 4 or 8 cycles of nivolumab

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:1 year
Safety Issue:
Description:Progression-free survival at 1 year; also to be analysed stratified by partial metabolic response vs complete metabolic response.
Measure:Overall survival
Time Frame:1 year
Safety Issue:
Description:Overall survival at 1 year; also to be analysed stratified by partial metabolic response (PMR) vs complete metabolic response (CMR).
Measure:Proportion of patients progressing to stem cell transplant
Time Frame:1 year
Safety Issue:
Description:Proportion of patients progressing to autologous or allogeneic stem cell transplant
Measure:Adverse events [Safety and toxicity of nivolumab]
Time Frame:3 years
Safety Issue:
Description:Adverse events and serious adverse events occurring in patients treated with nivolumab, in particular autoimmune toxicity
Measure:Transplant-related mortality
Time Frame:3 years
Safety Issue:
Description:Proportion of patients treated with nivolumab that subsequently die of transplant-related causes
Measure:Transplant-related morbidity
Time Frame:3 years
Safety Issue:
Description: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)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University College, London

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