A Study of BV-AVD in People With Bulky Hodgkin Lymphoma

Official title

BV-AVD in Patients With Newly-Diagnosed, Early Stage, Bulky Hodgkin Lymphoma Using a PET-adapted and MTV-guided Approach

Overview

The purpose of this study is to test whether BV-AVD is an effective treatment in people with early stage, bulky Hodgkin lymphoma that was recently diagnosed and who have not yet received any treatments for their disease. BV is a type of drug called an antibody-drug conjugate (ADC). ADCs are a substance made up of a monoclonal antibody chemically linked to a drug. Antibodies are proteins made by the immune system to fight infections and other possible harms to the body. The monoclonal antibody binds to specific proteins or receptors found on certain types of cells, including cancer cells. The linked drug enters these cells and kills them without harming other cells. Researchers think BV may be an effective treatment for this type of cancer because the drug targets cells that have CD30, which play a role in cancer cell growth. By destroying these cells, BV may help slow or stop the growth of the cancer. AVD (doxorubicin, vinblastine, and dacarbazine) is a treatment regimen that works by stopping the growth of cancer cells, either by killing the cells or by stopping them from dividing. The researchers think that BV in combination with AVD may work better than AVD alone to slow or stop the growth of the cancer.

Interventions

• Drug Brentuximab vedotin
  Brentuximab vedotin will be administered at 1.2 mg/kg IV on days 1 and 15 of each 28-day cycle
• Drug Doxorubicin
  Doxorubicin 25 mg/m\^2 IV
• Drug Vinblastine
  Vinblastine 6 mg/m\^2 IV
• Drug Dacarbazine
  Dacarbazine 375 mg/m\^2 IV on days 1 and 15 of each 28-day cycle
• Drug Pembrolizumab
  Pembrolizumab will be administered at 200 mg IV (flat) on day 1
• Drug Gemcitabine
  Gemcitabine 1000 mg/m\^2 IV (days 1 an
• Drug Vinorelbine
  Vinblastine 6 mg/m\^2 IV
• Diagnostic test FDG-PET/CT scan
  After 2 cycles of therapy, patients will undergo FDG-PET/CT scan

Primary outcome measures

• progression-free survival [Time frame: 3 years]

Secondary outcome measures (1)

• overall survival [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Histological diagnosis of classical, CD30-positive Hodgkin lymphoma confirmed at enrolling institution.
• Ann Arbor stage I or II FDG-avid disease by FDG-PET/CT.
• Disease bulk defined as any lymph node mass with transverse maximal diameter ≥ 7.0 cm or coronal maximal diameter ≥ 7.0 cm on CT imaging.
• Age 18 and over.
• ECOG Performance Status ≤ 2
• Females of childbearing age must be on an acceptable form of birth control per institutional standards during the treatment period.
• Males must consistently use an acceptable form of contraception per institutional standards during the treatment period.

Exclusion criteria

• Prior systemic therapy or radiation therapy for Hodgkin lymphoma (excluding corticosteroids)
• Cardiac ejection fraction < 50% as measured by echocardiogram.
• Platelet count ≤ 75,000/µL.
• Hemoglobin level ≤ 7.0 mg/dL.
• Absolute neutrophil count ≤ 1.0 K/µL.
• Serum creatinine clearance < 30 mL/minute as estimated by the Cockcroft-Gault Method.
• Transaminase levels > 3 times the upper limit of normal in the absence of a history of Gilbert's disease or hepatic involvement. In patients with Gilbert's disease, > 5 times the upper limit of normal is exclusionary.
• Total bilirubin ≥ 1.5 the upper limit of normal in the absence of a history of Gilbert's disease or hepatic involvement. In patients with Gilbert's disease, > 3 times the upper limit of normal is exclusionary.
• Pre-existing peripheral neuropathy ≥ grade 2 prior to participation.
• Known pregnancy or breast-feeding
• Active viral infection with hepatitis B or hepatitis C. For hepatitis B, patients who are seropositive (hepatitis B core Ab positive) are permitted if HBV DNA is negative by PCR. For hepatitis C, patients who are seropositive (hepatits C Ab positive) are eligible if HCV DNA is negative by PCR and curative therapy has been completed.
• Concurrent malignancy requiring active therapy within the last 2 years with the exception of basal cell or squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent is permitted.
• Patients with autoimmune conditions requiring active, ongoing systemic immunosuppressive therapy.
• Medical illness unrelated to Hodgkin lymphoma which in the opinion of the treating physician and/or principal investigator makes participation inappropriate.

Note: Patients with HIV infection are permitted to enroll but are required to be on antiretroviral regimens that are in accordance with the current International AIDS Society guidelines concurrently with chemotherapy. Use of experimental antiretroviral agents or those containing zidovudine or ritonavir, cobicistat or similar potent CYP3 inhibitors are prohibited. In order to be eligible, patients taking zidovudine or ritonavir, or cobicistat or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation. Subjects must be on HAART for at least 12 weeks prior to therapy.

Note: Patients with pre-existing autoimmune conditions are NOT excluded unless there is an autoimmune condition requiring active, ongoing systemic immunosuppressive therapy. However, careful consideration should be given to patients with pre-existing autoimmune conditions who may need pembrolizumab. Any concerns regarding patients with pre-existing autoimmune conditions and eligibility should be reviewed with the study PI.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• University of Miami — Miami
• Memorial Sloan Kettering Basking Ridge (All Protocol Activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale
• Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities) — Commack
• Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York
• Memorial Sloan Kettering Nassau (All Protocol Activities) — Uniondale

Identifiers

NCT: NCT06377566 · 24-039

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗