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

NCT ID: NCT02603419

Last Updated: 2020-04-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-10
• Study Completion Date: 2019-04-11

Brief 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.

Conditions

Hodgkins Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lead-in phase-Cohort A

X1 mg IV every 2 weeks

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Anti-PD-L1 antibody at X1 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.

Lead-in phase-Cohort B

X2 mg IV every 2 weeks

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Anti-PD-L1 antibody at X2 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.

Lead-in phase-Cohort C

X3 mg IV every 3 weeks

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Anti-PD-L1 antibody at X3 mg IV every 3 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression

Lead-in phase-Cohort D

X4 mg IV every 2 weeks

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Anti-PD-L1 antibody at X3 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression

Lead-in phase-Cohort E

X5 mg IV every 2 weeks

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Anti-PD-L1 antibody at X mg IV every 2 weeks. Treatment with avelumab will continue until disease progression

Expansion phase

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

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

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.

Interventions

Avelumab

Anti-PD-L1 antibody at X1 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.

Intervention Type: DRUG

Avelumab

Anti-PD-L1 antibody at X2 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.

Intervention Type: DRUG

Avelumab

Anti-PD-L1 antibody at X3 mg IV every 3 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression

Intervention Type: DRUG

Avelumab

Anti-PD-L1 antibody at X3 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression

Intervention Type: DRUG

Avelumab

Anti-PD-L1 antibody at X mg IV every 2 weeks. Treatment with avelumab will continue until disease progression

Intervention Type: DRUG

Avelumab

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 Type: DRUG

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

City of Hope

Duarte, California, United States

Az. Ospedaliera-Univers. di Bologna Policlinico S.Orsola-Malpighi

Bologna, BO, Italy

Istituto Clinico Humanitas U.O. Oncologia ed Ematologia

Rozzano, Milano, Italy

Q2 Solutions

Rosebank, Livingston, United Kingdom

Oxford University Hospitals NHS Foundation Trust

Headington, , United Kingdom

Leeds Teaching Hospital NHS Trust

Leeds, , United Kingdom

St James's University Hospital

Leeds, , United Kingdom

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

UCLH Clinical Research Facility

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Plymouth Hospitals NHS Trust, Derriford Hospital

Plymouth, , United Kingdom

Countries

United States; Italy; United Kingdom

References

Herrera AF, Burton C, Radford J, Miall F, Townsend W, Santoro A, Zinzani PL, Lewis D, Fowst C, Brar S, Huang B, Thall A, Collins GP. Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial. Blood Adv. 2021 Sep 14;5(17):3387-3396. doi: 10.1182/bloodadvances.2021004511.

Reference Type: DERIVED

PMID: 34477818 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pmiform.com/clinical-trial-info-request?StudyID=B9991007

To obtain contact information for a study center near you, click here.

Other Identifiers

2015-002636-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

JAVELIN HODGKINS

Identifier Type: OTHER

Identifier Source: secondary_id

JAVELIN HODGKIN'S

Identifier Type: OTHER

Identifier Source: secondary_id

B9991007

Identifier Type: -

Identifier Source: org_study_id