Avelumab In Patients With Previously Treated Advanced Stage Classical Hodgkin's Lymphoma (JAVELIN HODGKINS)

Pfizer

Status and phase: Terminated; Phase 1

Conditions: Hodgkins Lymphoma

Treatments: Drug: Avelumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02603419

JAVELIN HODGKINS (Other Identifier)

B9991007

JAVELIN HODGKIN'S (Other Identifier)

2015-002636-41 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34 participants in 6 patient groups

Lead-in phase-Cohort A

Experimental group

Description:

X1 mg IV every 2 weeks

Treatment:

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Lead-in phase-Cohort B

Experimental group

Description:

X2 mg IV every 2 weeks

Treatment:

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Lead-in phase-Cohort C

Experimental group

Description:

X3 mg IV every 3 weeks

Treatment:

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Lead-in phase-Cohort D

Experimental group

Description:

X4 mg IV every 2 weeks

Treatment:

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Lead-in phase-Cohort E

Experimental group

Description:

X5 mg IV every 2 weeks

Treatment:

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Expansion phase

Experimental group

Description:

X1 mg IV every 2 weeks followed by X1 or X4 mg every 2 weeks

Treatment:

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab

Drug: Avelumab