Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed Classical Hodgkin Lymphoma

  • STATUS
    Recruiting
  • End date
    Oct 15, 2023
  • participants needed
    31
  • sponsor
    City of Hope Medical Center
Updated on 25 March 2022

Summary

This phase II trial investigates how well brentuximab vedotin and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back (relapsed). 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. Nivolumab is an antibody that enhances the immune system to better fight Hodgkin lymphoma cells. Giving brentuximab vedotin and nivolumab may be able to defer stem cell transplant treatment and spare the considerable cost and toxicity on transplantation.

Description

PRIMARY OBJECTIVE:

I. Assess the durability of response to brentuximab vedotin (BV) plus nivolumab (nivo) by 24-month progression-free survival (PFS) in participants with 1st relapse of classical Hodgkin lymphoma (RcHL) who achieved early complete metabolic response (CMR) (CMR after 4 cycles).

SECONDARY OBJECTIVES:

I. Estimate CMR and overall response rate (ORR) after 4 cycles and at the end of BV-nivo therapy.

II. Estimate the PFS and overall survival (OS) for the entire cohort and for subgroups of patients defined by their response.

III. Estimate the PFS and OS separately for responders who did and did not receive radiotherapy.

IV. Evaluate the toxicities of BV-nivo in the study population.

EXPLORATORY OBJECTIVES:

I. Estimate the second PFS after salvage therapy for patients who progress after study therapy, and for the subset of these patients who proceeded to autologous stem cell transplant (ASCT).

II. Explore the association between clinical outcomes and pathological tumor characteristics.

III. Explore the association between clinical outcomes and circulating tumor deoxyribonucleic acid (ctDNA) characteristics (mutation profile, kinetics of clearance).

OUTLINE

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and 6, 12, 18, 24, 36, 48, and 60 months.

Details
Condition Recurrent Classic Hodgkin Lymphoma
Treatment Nivolumab, brentuximab vedotin
Clinical Study IdentifierNCT04561206
SponsorCity of Hope Medical Center
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Be willing to provide tissue (either from a fresh core or excisional biopsy performed
as standard of care, or from archival tissue) of a biopsy that was performed
If unavailable, exceptions may be granted with study principal investigator (PI) approval
Eastern Cooperative Oncology Group (ECOG) =< 2
after frontline systemic therapy, and prior to starting protocol therapy
Histologically confirmed diagnosis of classical Hodgkin lymphoma (excluding nodular lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
First relapse, defined as
No more than 1 line of prior therapy (not counting radiotherapy)
No primary refractory disease (i.e. patients cannot have relapsed within 90 days of the end of frontline therapy)
Patients who received BV or an anti-PD-1/PD-L1 agent as part of frontline therapy are eligible if they achieved a CMR with frontline therapy and have not relapsed within 6 months from the end of frontline therapy Relapse must have been confirmed histologically (with hematopathology review at the participating institution)
Measurable disease (at least one non-bony fludeoxyglucose F-18 [FDG]-avid lesion >= 1.5 cm in long axis)
Not a candidate for ASCT, based on age, co-morbidities, or patient preference. The
Absolute neutrophil count (ANC) >= 1,000/mm^3
reason for ASCT non-candidacy must be documented in the Case Report Form and
NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
verified by the site PI
Platelets >= 50,000/mm^3
NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
Hemoglobin >= 8 g/dL (no transfusion allowed within 3 days prior to screening)
Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< 1.5 x ULN for patients with Gilbert's disease
Aspartate aminotransferase (AST) =< 2.5 x ULN
Alanine aminotransferase (ALT) =< 2.5 x ULN
Creatinine clearance of >= 40 mL/min per 24 hour urine test or the Cockcroft-Gault formula
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Agreement by women and men of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months (women) or 7 months (men) after the last dose of protocol therapy
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria

Concomitant investigational therapy
Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, bacillus Calmette-Guerin [BCG], oral polio vaccine, and oral typhoid)
Grade >= 2 peripheral neuropathy
History of prior >= grade 3 hypersensitivity to either brentuximab vedotin or nivolumab
Known active central nervous system (CNS) involvement by lymphoma, including parenchymal and/or lymphomatous meningitis
History of another primary malignancy that has not been in remission for at least 3 years, with the following exceptions
Non-melanoma skin cancer treated with curative intent
In situ cervical cancer
If the malignancy is expected to not require any treatment for at least 2 years (this exception should be discussed with the study PI)
Inhaled or topical steroids and
Adrenal replacement doses > 10 mg daily prednisone equivalents in the absence of active autoimmune disease
History of progressive multifocal leukoencephalopathy (PML)
Condition requiring systemic treatment with either corticosteroids (> 10 mg daily
Prior diagnosis of inherited or acquired immunodeficiency
prednisone or equivalent) or other immunosuppressive medications within 14
Active pneumonitis or interstitial lung disease
days of study drug administration. Exceptions are
Active, known or suspected autoimmune disease. The following are exceptions
Vitiligo
Psoriasis not requiring systemic treatment
Hemolytic anemia associated with the lymphoma
Type I diabetes mellitus, if adequately controlled with therapy
Thyroid disease, if adequately controlled with therapy
Conditions not expected to recur in the absence of an external trigger (such exceptions should be discussed with the study PI)
Active history of
Hepatitis B (hepatitis B virus [HBV]) or C (hepatitis C virus [HCV]) infection. Patients with past HBV infection (defined as negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody [HBcAb]) are eligible if HBV DNA is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
Human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable human immunodeficiency virus (HIV) viral load with CD4 >= 200 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
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)
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 day 1 of protocol
therapy
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