Blinatumomab in Treating Patients with Relapsed or Refractory Non-Hodgkin Lymphoma

Inclusion Criteria

• Subjects must have histologically determined B cell NHL that is relapsed or primary refractory after initial therapy * Follicular lymphoma of any grade * Marginal zone lymphoma (extranodal, nodal, or splenic); patients with gastric mucosa-associated lymphoid tissue (MALT) must have progressed after Helicobacter pylori (H. pylori) therapy and radiation; patients with splenic marginal zone lymphoma (MZL) must have prior splenectomy
• At least 1 prior line of chemoimmunotherapy if primary refractory or relapsed within one year; subjects who respond to initial therapy for greater than one year must have had at least 2 prior lines of therapy including one line with chemoimmunotherapy including an anti-CD20 monoclonal antibody
• Measurable disease that has not been previously irradiated on positron emission tomography-computed tomography (PET-CT) of at least 1.5 cm
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 750/mcL
• Platelets >= 75,000/mcL
• Total bilirubin < 2.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x upper limit of normal or =< 5 x ULN if due to lymphoma infiltration
• Creatinine =< 2.0 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for participants with creatinine levels above 2.0 x ULN
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Participants who have had chemotherapy within 3 weeks, rituximab or obinutuzumab within 4 weeks, or radioimmunotherapy within 6 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier; subjects actively progressing within that window who have recovered from toxicities of prior therapy are also eligible
• Autologous stem cell transplantation within 12 weeks prior to study entry
• Prior allogeneic transplant
• Therapeutic doses of corticosteroids within 14 days prior to study entry, defined as > 20 mg/day of prednisone, or equivalent; topical and/or inhaled steroids are permitted
• Participants who are receiving any other investigational agents
• Participants with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to blinatumomab
• Subjects with known human immunodeficiency virus (HIV) infection
• Pregnant or lactating subjects
• Chronic infection with hepatitis B or hepatitis C virus
• History of or current relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis
• Prior history of another malignancy (except for non-melanoma skin cancer, in situ cervical or breast cancer, or localized prostate cancer) unless disease free for at least one year and felt at low risk of relapse by treating physician
• Uncontrolled intercurrent illness including, but not limited to, ongoing or uncontrolled systemic fungal, bacterial, viral, or other infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

PRIMARY OBJECTIVES:

I. Evaluate clinical efficacy of blinatumomab in relapsed/refractory indolent non-Hodgkin lymphoma (NHL).

SECONDARY OBJECTIVES:

I. Determine progression-free survival and duration of response.

II. Evaluate safety of blinatumomab in relapsed/refractory indolent NHL subjects.

EXPLORATORY OBJECTIVES:

I. Evaluate the impact of baseline B cell to T cell (B:T) lymphocytes ratio in peripheral blood on response and central nervous system (CNS) toxicity.

OUTLINE: This is a dose-escalation study.

Patients receive blinatumomab intravenously (IV) continuously on days 1-42 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for every 3 months for 2 years and then every 6 months for 3 years

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Jeffrey A. Barnes

• Primary ID 16-118
• Secondary IDs NCI-2016-01369
• Clinicaltrials.gov ID NCT02811679