Brentuximab Vedotin, Bendamustine, and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT02623920 | Withdrawn Phase 2 DMC

• 1 other identifier: 1507953455
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, use antibody to target chemotherapy in cancer cells. Drugs used in chemotherapy, such as bendamustine, work in different ways to kill cancer cells. Monoclonal antibodies, such as rituximab, kill the cancer cells directly, but also harness the immune system to kill the cancer cells. Adding brentuximab to rituximab may improve response rates in CD30 positive, CD20 positive Relapsed Refactory NHL.

Conditions

Diffuse Large B Cell Lymphoma; Mediastinal Large B-cell Lymphoma; Grey Zone Lymphoma; High Grade B Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• CR rate

  The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.

  Up to 2 years after completion of study treatment

• Percentage of patients obtaining a CR + PR using Cheson criteria

  The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.

  Up to 2 years after completion of study treatment

Secondary Outcomes (7)

• Median time to progression

  At 2 years

• PFS

  At 2 years

• Complete response rate assessed by PET/CT

  Up to 2 years after the completion of study treatment

• Frequency of adverse events (AEs) and serious AEs assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 2 years after completion of study treatment

• CD34+ peripheral blood stem cells assessed by flow cytometry

  Up to 2 years after completion of study treatment

Other Outcomes (3)

• CD30 expression by immunohistochemistry (IHC)

  Up to 2 years after completion of study treatment

• Genetic mutations identified by NGS

  Up to 2 years after completion of study treatment

• GEP by Nanostring Technology

  Up to 2 years after completion of study treatment

Study Arms (1)

Brentuximab, Bendamustine, Rituximab

EXPERIMENTAL

Brentuximab Vedotin in Combination with Bendamustine and Rituximab

Drug: Brentuximab; Drug: Bendamustine; Drug: Rituximab

Interventions

Brentuximab DRUG

Brentuximab vedotin IV over 30 minutes on day 1.Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Also known as: Brentuximab Vedotin, Adcetris

Brentuximab, Bendamustine, Rituximab

Bendamustine DRUG

Bendamustine IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Also known as: Treanda

Brentuximab, Bendamustine, Rituximab

Rituximab DRUG

Rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Also known as: Rituxan

Brentuximab, Bendamustine, Rituximab

Eligibility Criteria

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

You may qualify if:

• CD30 detectable B lineage relapsed refractory NHL including the following histologies:
• Aggressive lymphomas: diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, grey zone lymphomas, high grade B cell lymphomas, and transformed indolent lymphomas
• Indolent lymphoma: follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma; indolent lymphoma patients eligible for this trial should have high tumor burden and high risk disease, as defined by:
• The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
• Intermediate or high risk by Follicular Lymphoma International Prognostic Index (FLIPI) score or elevated lactose dehydrogenase (LDH)/ beta-2 microglobulin (B2M)
• Subjects between 18 and 75 years old. Subjects older than 75 years old to be discussed with PI prior to subject consent; consensus between PI and treating physician is required.
• Karnofsky performance status (KPS) \>= 70%, Eastern Cooperative Oncology Group (ECOG) =\< 2
• At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
• Patients must have received at least one but no more than 4 prior lines of systemic therapy
• American Heart Association (AHA) class 1 without significant limitation of physical activity
• Ejection fraction (EF) of at least \>= 40% by multigated acquisition (MUGA) or echocardiography (ECHO)
• Total bilirubin =\< 1.5 mg/dl
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 2.5 times the upper limit of normal without evidence of active infectious hepatitis
• Creatinine clearance \>= 40 ml/min
• Platelets \> 75,000 cells/ul

You may not qualify if:

• Active infections (bacterial, fungal, or viral)
• Evidence of sanctuary site involvement by disease, e.g., central nervous system, ocular, testicular involvement
• Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
• Recent chemotherapy within 3 weeks of screening
• Major surgery within 4 weeks of screening
• Diagnosed or treated for malignancy other than NHL for which patient will be treated, except: malignancy treated with curative intent and with no known active disease present for \>= 3 years before subject registration; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease
• History of stroke or intracranial hemorrhage within 6 months prior to registration
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists
• Requires treatment with strong cytochrome (CYP3A4/5) inhibitors
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
• Women who are pregnant or breastfeeding
• Prior use of brentuximab vedotin
• Prior use of bendamustine for indolent lymphoma allowed if \> 2 years, CR to bendamustine and well tolerated with no residual \> grade 1 toxicity; no prior use of bendamustine for aggressive lymphoma allowed
• Prior allogeneic transplant

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

Arizona Cancer Center at UMC North

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Brentuximab Vedotin; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; 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; Antibodies, Monoclonal, Murine-Derived

Study Officials

• Daniel O. Persky, MD

  University of Arizona

  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

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: December 8, 2015
• Study Start: December 16, 2015
• Primary Completion: May 17, 2017
• Study Completion: May 17, 2017
• Last Updated: May 19, 2017

Record last verified: 2017-05

Locations

US (1)