Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients with Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

Protocol: OSU-16161

Full Title

A Phase I Trial of MEDI-570 in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) Follicular Variant and Angioimmunoblastic T-Cell Lymphoma (AITL)

Purpose

This phase I trial studies the side effects and best dose of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570 in treating patients with peripheral T-cell lymphoma follicular variant or angioimmunblastic T-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Monoclonal antibodies, such as MEDI-570, may block cancer growth in different ways by targeting certain cells.

Study Objective

PRIMARY OBJECTIVES:

I. To determine the safety, maximum tolerated dose and recommended phase II dose (RP2D) of MEDI-570 (anti-ICOS monoclonal antibody MEDI-570) in patients with refractory/relapsed peripheral T-cell lymphoma (PTCL) follicular variant and angioimmunoblastic T-cell lymphoma (AITL).

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity.

II. To evaluate the pharmacokinetic profile of MEDI-570.

III. To evaluate the overall response rate (ORR), disease control and progression free survival (PFS) of MEDI-570.

TERTIARY OBJECTIVES:

I. To evaluate biomarkers of response and resistance to MEDI-570 in the study population.

OUTLINE: This is a dose-escalation study.

Patients receive anti-ICOS monoclonal antibody MEDI-570 intravenously (IV) over 1-4 hours on day 1. Treatment repeats every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 weeks for 12 weeks.

Are you eligible?

Inclusion Criteria:

Patients must have histologically or pathologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) follicular variant or angioimmunoblastic T-cell lymphoma (AITL) as per World Health Organization (WHO) 2008 criteria

At least 28 days from the last therapy dose, and resolution of toxicity related to the last therapy, excluding grade 2 or less peripheral neuropathy and alopecia; for radiation therapy, a minimum of 2 weeks and resolution of all acute toxicity will be required

Must have refractory/relapsed disease to at least one line of therapy

Patients must have at least one measurable lesion that can be accurately measured in at least one dimension as >= 1.5 cm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, or physical exam (by calipers only); patients will be assessed on this study using the Lugano criteria for the evaluation of lymphomas

Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

Life expectancy of greater than 6 months

Leukocytes >= 3,000/mcL

Hemoglobin >= 90 d/L (or >= 9g/dL)

Absolute neutrophil count >= 1,500/mcL

Platelets >= 75,000/mcL

Absolute CD4 count > 200 cells/uL

Total bilirubin < 1.5 upper limit of normal (ULN)

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal

Creatinine < 1.5 mg/dl (= 132 umol/L) or

Creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

Availability of tissue for correlative studies; patients must have at least 6-8 unstained slides of archived formalin-fixed, paraffin-embedded tumor tissue available; if not enough archived tissue is available, a fresh tumor biopsy prior to study initiation is mandatory; for patients who have undergone a fresh baseline biopsy at baseline, the archived tissue is not mandatory

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, during the study participation, and for 3 months after the last dose of the drug; 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; men treated or enrolled on this protocol must have either had a prior vasectomy or agree to use effective contraception prior to the study, during the study, and for 3 months after the last dose of the drug; males should avoid fathering children during and for at least three months after therapy is completed

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients who have had chemotherapy or other systemic anticancer treatments within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

Patients who have had radiation therapy within 2 weeks prior to entering the study

Patients who are receiving any other investigational agents

Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

History of allergic reactions attributed to compounds of similar chemical or biologic composition to MEDI-570

Any history or evidence of opportunistic infection within 6 months of screening including tuberculosis, severe cytomegalovirus (CMV) or herpetic infections (such as disseminated herpes, herpes encephalitis, ophthalmic herpes)

Evidence of infection at any time with hepatitis B or C virus or human immunodeficiency virus (HIV)-1 or HIV-2; patients will be tested at the time of screening

History of primary immunodeficiency

Evidence of active or latent tuberculosis (TB)

Patients who have undergone allogeneic stem cell transplantation

Patients who have undergone autologous stem cell transplantation within 3 months from study entry

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MEDI-570; breastfeeding should be discontinued if the mother is treated with MEDI-570

HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential effects on immunosuppression. Additional T-cell immunosuppression in HIV-positive patients will place them at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Lymphoma Non-Hodgkin’s Lymphoma (B- & T-Cell)