Brentuximab Vedotin and Bendamustine for the Treatment of Relapsed or Refractory Follicular Lymphoma

NCT04587687 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: UCDCC#284NCI-2020-06645P30CA093373
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial investigates how well brentuximab vedotin and bendamustine work in treating patients with follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). 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. Chemotherapy drugs, such as bendamustine, 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. This trial is being done to determine if the combination of brentuximab vedotin plus bendamustine is safe and to determine the effectiveness of the combination.

Conditions

Recurrent Follicular Lymphoma; Refractory Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• Complete response (CR) rate

  Will be assessed per 2014 Lugano criteria and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria. Will be summarized with 95% confidence intervals.

  Up to 2 years

• Best overall response rate (ORR)

  Will be assessed by complete response + partial response per 2014 Lugano criteria and LYRIC criteria.

  Up to 2 years

Secondary Outcomes (4)

• Duration of response

  From time of initial response assessment demonstrating at least partial response until disease response assessment that demonstrates progressive disease, assessed up to 2 years

• Time to response

  From registration to first disease response assessment that demonstrates at least partial response, assessed up to 2 years

• Progression-free survival

  From registration until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow-up, whichever comes first, assessed up to 2 years

• Overall survival

  From registration to death due to any cause, assessed up to 2 years

Study Arms (1)

Treatment (brentuximab vedotin, bendamustine)

EXPERIMENTAL

Patients receive brentuximab vedotin IV over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Bendamustine Hydrochloride; Drug: Brentuximab Vedotin

Interventions

Bendamustine Hydrochloride DRUG

Given IV

Also known as: Bendamustin Hydrochloride, Bendeka, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treanda

Treatment (brentuximab vedotin, bendamustine)

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Treatment (brentuximab vedotin, bendamustine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed relapsed or refractory follicular CD30+ non-Hodgkin lymphoma (NHL) (included in this category are follicular grade I, II, IIIa). CD30 positivity \> 1% (tumor cells or surrounding peripheral microenvironment)
• Patients must have measurable disease by computed tomography (CT) or positron emission tomography (PET) scan, with one or more sites of disease \>= 1.5 cm in longest dimension
• Relapsed or refractory disease after at least 1 prior regimen, defined using the 2014 Lugano classification
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Leukocytes \>= 2,500/mcL
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 50,000/mcL
• Hemoglobin \>= 8 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement)
• Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)
• Creatinine clearance \>= 30 mL/min/1.73 m\^2 by Cockcroft-Gault
• Institutional normalized ratio (INR) and partial thromboplastin time (aPTT) =\< 1.5 x ULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose.)
• Administration of bendamustine or brentuximab vedotin may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Patients who have had chemotherapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C, steroid treatment for follicular lymphoma is allowed per protocol) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 2 weeks earlier. Specifically, the following therapies are not allowed:
• Herbal therapy (1 week washout required)
• Treatment with any other investigational agent within 3 weeks prior to cycle 1, day 1.
• Prior therapy with bendamustine or a bendamustine-containing regimens with progression within 6 months of receiving treatment
• Current or prior use of immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 14 days prior to first dose (cycle 1, day 1). The following are exceptions to this criterion:
• Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10 mg/day of prednisone or equivalent may be enrolled
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
• Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
• Patients with known uncontrolled central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
• History of hypersensitivity to bendamustine or brentuximab vedotin or any excipient
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.

Sponsors & Collaborators

• Joseph Tuscano: lead
• National Cancer Institute (NCI): collaborator
• Seagen Inc.: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Bendamustine Hydrochloride; Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Joseph M Tuscano

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 14, 2020
• Study Start: December 4, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

US (1)