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

Conditions

• Recurrent Classic Hodgkin Lymphoma
• Refractory Classic Hodgkin Lymphoma

Eligibility Criteria

Sex

ALL

Age

5 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• 3-Dimensional Conformal Radiation Therapy — RADIATION
  Undergo 3DCRT
• Autologous Hematopoietic Stem Cell Transplantation — PROCEDURE
  Undergo ASCT
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Brentuximab Vedotin — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT and PET/CT
• High Dose Chemotherapy — DRUG
  Receive HDT
• Intensity-Modulated Radiation Therapy — RADIATION
  Undergo IMRT
• Nivolumab — BIOLOGICAL
  Given IV
• Pembrolizumab — BIOLOGICAL
  Given IV
• Pencil Beam Scanning — RADIATION
  Undergo pencil beam proton RT
• Positron Emission Tomography — PROCEDURE
  Undergo PET/CT
• Salvage Therapy — PROCEDURE
  Receive standard of care salvage therapy
• Scattering Proton Beam Therapy — RADIATION
  Undergo passive scattering proton RT
• Tomotherapy — RADIATION
  Undergo tomotherapy
• Uniform Active Scanning Proton Beam Therapy — RADIATION
  Undergo uniform scanning proton RT
• Volume Modulated Arc Therapy — RADIATION
  Undergo VMAT

Study Details

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.

Key Dates

Start date

Dec 4, 2026

Status verified

May 2026

Primary completion

Mar 31, 2029

Completion

Mar 31, 2029

Study Design

Enrollment

374 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A (salvage therapy, RT, brentuximab vedotin, nivolumab)
  Patients receive 2-4 cycles of standard of care salvage therapy per investigator choice. Patients undergo photon RT with either 3DCRT, IMRT, VMAT, or tomotherapy or proton RT with either passive scattering, uniform scanning, or pencil beam scanning over 15-17 fractions. Starting 4-8 weeks after completing radiation therapy, patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab for an additional 2 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo blood sample collection, CT, and PET/CT throughout the study.
• Experimental: Arm B (salvage therapy, HDT-ASCT, RT, brentuximab vedotin[BV])
  Patients receive 2-4 cycles of standard of care salvage therapy per investigator choice. Patients receive HDT and undergo ASCT per standard of care in the absence of disease progression or unacceptable toxicity. Starting within 4-8 weeks after transplant, patients with CMR may also undergo RT as in arm A over 15-17 fractions and patients with PMR may also undergo RT over 20-22 fractions per investigator. Starting 30-45 days after transplant, patients may also receive maintenance treatment with brentuximab vedotin for up to 16 cycles in the absence of disease progression or unacceptable toxicity as determined per investigator at time of randomization. Additionally, patients may undergo blood sample collection, CT, and PET/CT throughout the study.
• Experimental: Arm C (salvage therapy, HDT-ASCT, pembrolizumab, RT, BV)
  Patients receive 2-4 cycles of standard of care salvage therapy per investigator choice. Patients receive HDT and undergo ASCT per standard of care. Starting 4-8 weeks after transplant, patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Starting within 4-8 weeks after transplant, patients with CMR may also undergo RT as in arm A over 15-17 fractions and patients with PMR may also undergo RT over 20-22 fractions per investigator. Starting 30-45 days after transplant, patients may also receive maintenance treatment with brentuximab vedotin for up to 16 cycles in the absence of disease progression or unacceptable toxicity as determined per investigator at time of randomization. Additionally, patients may undergo blood sample collection, CT, and PET/CT throughout the study.
• Experimental: Arm D (salvage therapy, HDT-ASCT, RT, brentuximab vedotin)
  Patients receive 2-4 cycles of standard of care salvage therapy per investigator choice. Patients receive HDT and undergo ASCT per standard of care in the absence of disease progression or unacceptable toxicity. Starting within 4-8 weeks after transplant, patients with CMR may also undergo RT as in arm A over 15-17 fractions and patients with PMR may also undergo RT over 20-22 fractions per investigator. Starting 30-45 days after transplant, patients may also receive maintenance treatment as in arm B in the absence of disease progression or unacceptable toxicity as determined per investigator at time of randomization. Additionally, patients may undergo blood sample collection, CT, and PET/CT throughout the study.

Primary Outcome Measure

Progression-free survival (PFS) (Standard risk cohort) [ Time Frame: From randomization to progression or death without documented progression, assessed up to 15 years ]

Related Studies

• Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors
  PHASE2 · Recruiting · Emory University · Atlanta, Georgia