A Study of BV-AVD in People With Bulky Hodgkin Lymphoma
This phase II trial tests how well brentuximab vedotin, doxorubicin, vinblastine and dacarbazine work to treat patients with early stage bulky 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. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell’s DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Chemotherapy drugs, such as vinblastine and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin, doxorubicin, vinblastine and dacarbazine may work better in treating patients with early stage, bulky Hodgkin lymphoma.
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
- Eastern Cooperative Oncology Group (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/uL
- Hemoglobin level ≤ 7.0 mg/dL
- Absolute neutrophil count ≤ 1.0 K/uL
- 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 hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is negative by polymerase chain reaction (PCR). For hepatitis C, patients who are seropositive (hepatitis C Ab positive) are eligible if hepatitis C virus (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 human immunodeficiency virus (HIV) infection are permitted to enroll but are required to be on antiretroviral regimens that are in accordance with the current International Acquired Immunodeficiency Syndrome (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 highly active antiretroviral therapy (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 principal investigator (PI).
Additional locations may be listed on ClinicalTrials.gov for NCT06377566.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
PRIMARY OBJECTIVE:
I. Determine the 3-year progression-free survival for patients with positron emission tomography 2 (PET2) negative early stage, bulky hodgkin lymphoma (HL) treated with brentximab vedotin, doxorubicin, vinblastine, dacarbazine (BV-AVD) x 4 cycles.
SECONDARY OBJECTIVES:
I. Evaluate the 3-year overall survival for patients with PET2 negative early stage, bulky HL treated with BV-AVD x 4 cycles.
II. Evaluate the 2-year progression-free survival for patients with PET2 negative early stage, bulky HL treated with BV-AVD x 4 cycles.
III. Evaluate PET-CR rate after 2 and 4 cycles of BV-AVD.
IV. Evaluate the prognostic significance (correlation with progression-free survival) of plasma cell-free deoxyribonucleic acid (DNA) and serum thymus and activation-regulated chemokine at baseline and prior to cycle 3.
V. Assess-treatment related toxicity.
EXPORATORY OBJECTIVES:
I. Summarize the response rates for patients with PET2 positive early stage, bulky HL.
II. Summarize 3-year and 2-year progression-free survival, and 3-year overall survival for patients with PET2 positive early stage, bulky HL.
OUTLINE:
Patients receive bretuximab vedotin intravenously (IV), doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for 2 cycles. Patients then undergo disease evaluation and are assigned to 1 of 3 groups based on response. Patients with complete response (CR) are assigned to group I, patients with partial response (PR) or stable disease (SD) with a low baseline metabolic tumor volume (bMTV) are assigned to group II, patients with PR or SD and a high bMTV are assigned to group III and patients with progressive disease are taken off study.
GROUP I (CR): Patients receive 2 additional cycles of brentuximab vedotin, doxorubixin, vinblastine and dacarbazine as described above in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or multigated aquisition (MUGA) scan during screening, fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) scan throughout the study, blood sample collection on study and computed tomography (CT) scan during follow up.
GROUP II (PR/SD low bMTV): Patients receive 2 additional cycles of brentuximab vedotin, doxorubixin, vinblastine and dacarbazine as described above in the absence of disease progression or unacceptable toxicity and complete radiation therapy, 5 days per week for 3 weeks, for a total of 15 treatments. Patients undergo echocardiography or MUGA scan during screening, FDG PET/CT scan throughout the study, blood sample collection on study and CT scan during follow up.
GROUP III (PR/SD high bMTV): Patients receive pembrolizumab IV on day 1, and gemcitabine IV, vinorelbine IV, and liposomal doxorubicin IV on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 4 cycles followed by radiation therapy 5 days per week for 3 weeks, for a total of 15 treatments. Patients undergo echocardiography or MUGA scan during screening, FDG PET/CT scan throughout the study, blood sample collection on study and CT scan during follow up.
After completion of study treatment, patients are followed up at 4 weeks and every 6 months for up to 5 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorRobert Stuver
- Primary ID24-039
- Secondary IDsNCI-2024-03567
- ClinicalTrials.gov IDNCT06377566