Evaluating the Addition of Maintenance Immunotherapy Compared to the Usual Treatment of Chemotherapy and Autologous Stem Cell Transplant Alone for High-risk Patients With Relapsed or Refractory Hodgkin Lymphoma

Summary

This phase II trial compares the impact of brentuximab vedotin and nivolumab after radiation to standard of care high dose chemotherapy (HDT)-autologous stem cell transplant (ASCT) in standard-risk patients with classic Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). In addition, the phase III trial will compare the effect of pembrolizumab after HDT-ASCT to standard of care HDT-ASCT alone in high-risk patients with relapsed or refractory classic Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. An ASCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving HDT before an ASCT helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Radiation therapy (RT) uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving brentuximab vedotin and nivolumab after radiation may be safe, tolerable and more effective than standard of care HDT-ASCT in treating patients with standard risk relapsed or refractory classic Hodgkin lymphoma. In addition, giving pembrolizumab after standard of care HDT-ASCT may be safe and tolerable and more effective than HDT-ASCT alone in treating high-risk patients with relapsed or refractory classic Hodgkin lymphoma.

Conditions

• Recurrent Classic Hodgkin Lymphoma
• Refractory Classic Hodgkin Lymphoma

Interventions

RADIATION

3-Dimensional Conformal Radiation Therapy

Undergo 3DCRT

PROCEDURE

Autologous Hematopoietic Stem Cell Transplantation

Undergo ASCT

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

DRUG

Brentuximab Vedotin

Given IV

PROCEDURE

Computed Tomography

Undergo CT and PET/CT

DRUG

High Dose Chemotherapy

Receive HDT

RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT

BIOLOGICAL

Nivolumab

Given IV

BIOLOGICAL

Pembrolizumab

Given IV

RADIATION

Pencil Beam Scanning

Undergo pencil beam proton RT

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

PROCEDURE

Salvage Therapy

Receive standard of care salvage therapy

RADIATION

Scattering Proton Beam Therapy

Undergo passive scattering proton RT

RADIATION

Tomotherapy

Undergo tomotherapy

RADIATION

Uniform Active Scanning Proton Beam Therapy

Undergo uniform scanning proton RT

RADIATION

Volume Modulated Arc Therapy

Undergo VMAT

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Vaishalee P Kenkre · ECOG-ACRIN Cancer Research Group

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-12-04

Primary Completion

2029-03-31

Completion

2029-03-31

FDA Drug

Yes