Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma

Classic Hodgkin Lymphoma Clinical Trial

Official title:

A Phase 2 Front-Line PET/CT-2 Response-Adapted Brentuximab Vedotin and Nivolumab Incorporated and Radiation-Free Management of Early Stage Classical Hodgkin Lymphoma (cHL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03712202
• Other study ID #: 18157
• Secondary ID: NCI-2018-0159218
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 28, 2018
• Est. completion date: September 23, 2024

Study information

• Verified date: April 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Description:

PRIMARY OBJECTIVE:

I. Determine the 18-month progression free survival (PFS) for each arm of therapy stratified by positron emission tomography (PET)/computed tomography (CT)-2 response.

SECONDARY OBJECTIVES:

I. Assess safety, tolerability, and quality of life (QOL) for each arm of therapy.

II. Measure PET/CT-2 negativity rate after 2 lead-in cycles of standard of care doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD).

III. Evaluate the 3-year PFS and overall survival (OS) for each arm of treatment.

EXPLORATORY OBJECTIVES:

I. Evaluate if a baseline antitumor immune response, as assessed by a Nanostring gene panel, correlates with PFS.

II. Evaluate if minimal residual disease (MRD) status, as monitored by cancer personalized profiling by deep sequencing (CAPP-Seq) of circulating tumor (ct) deoxyribonucleic acid (DNA), can be correlated with PFS.

OUTLINE: Patients are assigned to 1 of 2 groups based on their PET/CT-2 scans.

GROUP I (PET/CT-2 NEGATIVE): Patients without bulky disease are randomized to either Arm A or B and patients with bulky disease are assigned to Arm B.

ARM A: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II (PET/CT-2 POSITIVE): Patients receive doxorubicin IV, vinblastine IV, dacarbazine, IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 155
• Est. completion date: September 23, 2024
• Est. primary completion date: September 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative.

• Assent, when appropriate, will be obtained per institutional guidelines.

• Eastern Cooperative Oncology Group (ECOG) =< 2.

• Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) by current World Health Organization classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, or classical Hodgkin lymphoma, NOS [not otherwise specified]) at local enrolling center. Nodular lymphocyte-predominant Hodgkin lymphoma is excluded

• Stage IA, IB, IIA, or IIB cHL by Cotswold modified Ann Arbor staging done prior to any treatment with ABVD.

• Must have prior to standard of care ABVD treatment at least one lesion that is > 1.5 cm in the longest diameter on cross-sectional imaging and measureable in two perpendicular dimensions on CT and fludeoxyglucose (FDG) avid by PET.

Exclusion Criteria:

• Patients must be naive in terms of any prior therapy for Hodgkin lymphoma (including immunotherapy, chemotherapy or radiation therapy) with the exception that they may have received up to 2 cycles of ABVD as standard of care therapy prior to enrollment, as long as they can start protocol therapy (therapy administered in Arms A, B1/B2, or C) within timelines specified by the trial.

• Peripheral sensory neuropathy > grade 1 or any peripheral motor neuropathy.

• History of another primary malignancy that has not been in remission for at least 3 years. (The following are exempt from the 3-year limit: nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolau [PAP] smear)

• Known cerebral/meningeal disease.

• History of progressive multifocal leukoencephalopathy (PML).

• Known history of pancreatitis.

• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to enrollment

• Uncontrolled cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 45%, coronary artery disease, or arrhythmias.

• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin, nivolumab, or any component of ABVD.

• Known active infection with hepatitis B or hepatitis C. Patients who are hepatitis B carriers can enroll if have a negative hepatitis B polymerase chain reaction (PCR) DNA test and are on hepatitis B suppressive medication management with entecavir or lamivudine. Patients with past active hepatitis C virus (HCV) infection are eligible if they are PCR negative after curative therapy. Testing to be done only in patients suspected of having infections or exposures.

• Known active infection with human immunodeficiency virus (HIV). Patients who are HIV positive can enroll if CD4 count is > 200/uL and have an undetectable or unquantifiable HIV viral load within 28 days of enrollment, have concurrent management with infectious disease specialists, and are on stable combination antiretroviral therapy. Participants are required to be on antiretroviral regimens that are in accordance with the current International acquired immune deficiency syndrome (AIDS) Society guidelines concurrently with chemotherapy. The specific agents are at the discretion of the Investigator and the use of investigational agents currently available on an expanded access basis is allowed. Use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir (includes Norvir or Kaletra), Cobicistat, Didanosine (Videx or Videx EC), or similar potent CYP3 inhibitors are prohibited. In order to be eligible, participants taking zidovudine or ritonavir, Cobicistat, Didanosine, or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation. Changes to highly active antiretroviral therapy (HAART) therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.). Participants must be on HAART for at least 7 days prior to therapy. HIV testing to be done only in patients suspected of having infections or exposures

• Subjects with active interstitial pneumonitis.

• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

• Females only: pregnant or breastfeeding.

• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Related Conditions & MeSH terms

• Ann Arbor Stage I Hodgkin Lymphoma
• Ann Arbor Stage I Lymphocyte-Depleted Classic HL
• Ann Arbor Stage I Mixed Cellularity Classic Hodgkin Lymphoma
• Ann Arbor Stage I Nodular Sclerosis Classic Hodgkin Lymphoma
• Ann Arbor Stage IA Hodgkin Lymphoma
• Ann Arbor Stage IB Hodgkin Lymphoma
• Ann Arbor Stage II Hodgkin Lymphoma
• Ann Arbor Stage II Lymphocyte-Depleted Classic HL
• Ann Arbor Stage II Mixed Cellularity Classic HL
• Ann Arbor Stage II Nodular Sclerosis Classic HL
• Ann Arbor Stage IIA Hodgkin Lymphoma
• Ann Arbor Stage IIB Hodgkin Lymphoma
• Classic Hodgkin Lymphoma
• Hodgkin Disease
• Lymphocyte-Rich Classic Hodgkin Lymphoma
• Lymphoma
• Sclerosis

Intervention

Drug:
• Bleomycin
Given IV
• Brentuximab Vedotin
Given IV
• Dacarbazine
Given IV
• Doxorubicin
Given IV

Biological:
• Nivolumab
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Drug:
• Vinblastine
Given IV

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	M D Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of California San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	18-month Progression-free survival (PFS) for each arm of therapy	Will be estimated using the method of Kaplan and Meier.	Up to 18 months
Secondary	Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0	Frequency tables will be used to summarize toxicity profile.	Up to 3 years
Secondary	Scores from European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire C30, version 3 (EORTC-C30) for each arm of therapy	All of the scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.	Up to 3 years
Secondary	Positron emission tomography/computed tomography-2 negativity rate	Will be estimated using the Deauville 5-point score/2014 Lugano Classsification	After 2 courses of ABVD (each course is 28 days)
Secondary	3-year PFS for each arm of treatment	Will be estimated using the method of Kaplan and Meier.	Up to 3 years
Secondary	Overall survival for each arm of treatment	Will be estimated using the method of Kaplan and Meier.	Up to 3 years