Avelumab In Patients With Previously Treated Advanced Stage Classical Hodgkin's Lymphoma (JAVELIN HODGKINS)
Condition: Hodgkins Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Avelumab; Avelumab; Avelumab; Avelumab; Avelumab; Avelumab
Intervention description: Anti-PD-L1 antibody at X1 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.; Anti-PD-L1 antibody at X2 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.; Anti-PD-L1 antibody at X3 mg IV every 3 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression; Anti-PD-L1 antibody at X3 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression; Anti-PD-L1 antibody at X mg IV every 2 weeks. Treatment with avelumab will continue until disease progression; Anti-PD-L1 antibody at X1 mg IV every 2 weeks which can be escalated to X4 mg every 2 weeks based on safety and efficacy. Treatment with avelumab will continue until disease progression.
Intervention MeSH terms: Avelumab; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: classical Hodgkins Lymphoma (relapsed/refractory); post-allogeneic HSCT; anti PD-L1; Phase 1; PK; Receptor occupancy; Immunophenotypic biomarkers

Summary:

      This is a Phase 1b, open-label, multi-center study comprising a lead-in phase and an
      expansion phase. The lead-in phase is a multiple-dose, randomized, parallel-arm,
      pharmacokinetic and pharmacodynamic study of avelumab as a single agent in adult patients
      with cHL. Patients enrolled in the lead-in phase of this study are required to have relapsed
      following a prior autologous or allogeneic HSCT, or to be ineligible for HSCT. Based on the
      preliminary TO, safety, and efficacy results from the lead-in phase, the expansion phase will
      evaluate the anti-tumor activity and safety of single-agent avelumab utilizing an
      intra-patient dose escalation paradigm based on two of the dosing regimens studied in the
      lead-in phase in 40 cHL patients in whom an allogeneic HSCT has failed.
    

Eligibility criteria:

        KEY INCLUSION CRITERIA

          -  Histological confirmation of classical Hodgkin's Lymphoma (cHL) with relapsed or
             refractory disease who, for the lead-in phase, either have had a prior autologous or
             allogeneic HSCT or are not eligible for HSCT, and , for the expansion phase, have had
             a prior allogeneic HSCT. In the expansion phase there must be a documented CD3+ donor
             chimerism of ≥20%.

          -  Patients must be off previous cHL therapy for at least 28 days prior to randomization
             in the lead-in phase/first dose of study treatment in the expansion phase.

          -  At least 1 fluorodeoxyglucose (FDG) PET avid (Deauville 4/5) measurable lesion >1.5 cm
             on PET-CT scan as defined by the Response Criteria for Malignant Lymphoma (for the
             lead-in phase) and the Lugano Classification (for the expansion phase) that has not
             previously been irradiated.

          -  Expansion phase: Required "de novo" or "archival" tumor biopsy, as well as required on
             treatment biopsy

          -  Estern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

        KEY EXCLUSION CRITERIA

          -  Patients with prior allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) who
             have had:

               1. Lead-in phase: allo HSCT performed <12 months prior to randomization. Expansion
                  phase: allo-HSCT performed ≤4 months prior to the first dose of study treatment.
                  NOTE: Patients who have had allo-HSCT performed >4 months prior to the first dose
                  of study treatment must have discontinued all immunosuppressive therapy, and must
                  have no clinical evidence of GVHD; or

               2. Immunosuppressive treatment for acute or chronic GVHD within 3 months prior to
                  randomization for the lead-in phase or prior to the first dose of study treatment
                  for the expansion phase (with the exception of those patients who required 15
                  mg/day oral prednisone or equivalent). Patients who required 15 mg/day oral
                  prednisone or equivalent must have discontinued it within 7 days prior to first
                  dose of study treatment; or

               3. Acute Grade 3 or Grade 4 GVHD at any time in the past (as defined by the modified
                  Seattle Glucksberg criteria (Consensus Conference on Acute GVHD Grading
                  Criteria); or

               4. Prior chronic GVHD (as defined by the NIH Consensus Development Project) that
                  persisted for >6 months and required systemic immunosuppression (with the
                  exception of those patients who required 15 mg/day oral prednisone or
                  equivalent). Patients who required 15 mg/day oral prednisone or equivalent must
                  have discontinued it within 7 days prior to the first dose of study treatment; or

               5. A donor lymphocyte infusion (DLI) within 3 months prior to randomization for the
                  lead-in phase or first dose of study treatment for the expansion phase.

          -  Prior therapy with an anti PD 1 or anti PD L1 mAb.

               1. Lead-in Phase: May be enrolled if patient stopped prior anti PD1 or anti-PD-L1
                  therapy more than one year prior to randomization and had a documented prior
                  response.

               2. Expansion Phase: Prior therapy with an anti-PD-1 or anti-PD-L1 agent following
                  allo-HSCT is prohibited unless the therapy was stopped more than one year prior
                  to the first dose of study treatment, and the patient had a documented prior
                  response. NOTE: Prior therapy with an anti-PD-1 or anti-PD-L1 agent prior to
                  allo-HSCT is permitted with no time limits and irrespective of a documented
                  response.

               3. Patients with a history of ≥Grade 3 anti-PD-1 or anti-PD-L1-related immune
                  toxicity are not eligible.