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

  • Interventional
  • Recruiting
  • NCT02520791
Eligibility Details Visit Clinicaltrials.gov

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)

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 anti-ICOS monoclonal antibody MEDI-570, may block cancer growth in different ways by targeting certain cells.

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-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), follicular lymphoma. mycosis fungoides (MF) and cutaneous T-cell lymphomas (CTCL).

     SECONDARY OBJECTIVES:

     I. To evaluate the pharmacokinetic profile of MEDI-570. II. To evaluate the overall response rate (ORR) and progression free survival (PFS) of MEDI-570 at all dose levels and in a 10-patient expansion cohort at the maximum tolerated dose (MTD).

     III. To determine short and long term effects of MEDI-570 at all dose levels on the immune system and on T-cell lymphocyte subsets.

     IV. To determine the relationship between ICOS expression on tumor cells and response to 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.

Gender
All

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

Inclusion Criteria:

         - Pathologic diagnosis of one of the following:

             - For dose escalation:

             - Confirmed diagnosis of peripheral T-cell lymphoma (PTCL) or angioimmunoblastic T-cell lymphoma (AITL) that is refractory to at least one line of therapy; anaplastic large cell lymphoma (ALCL) and natural killer T-cell lymphoma nasal type (NKTCL) are excluded

             - Advanced stage cutaneous T-cell lymphoma (CTCL), specifically CTCL NOS, small/medium T-cell lymphoma (SMTCL) and mycosis fungoides (MF) stage IB, IIA, IIB, III and IV that have relapsed after at least one specific prior therapy (e.g. interferon, photopheresis, denileukin difitox, bexarotene, etc); anaplastic cutaneous large cell lymphoma (ACLCL) and lymphomatoid papulopsis are excluded

             - Follicular lymphoma grade 1, 2 or 3A that meets the following criteria:

             - Relapsed or refractory to at least 2 lines of therapy AND

             - Relapsed or refractory post autologous cell transplantation (HCT)

             - For dose expansion/dose confirmation phase:

             - Patients with confirmed diagnosis of peripheral T-cell lymphoma (PTCL) follicular type or angioimmunoblastic T-cell lymphoma (AITL) that is refractory to at least one line of therapy

         - At least 14 days from the last therapy dose or 5 half-lives (whichever is shorter), 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

         - Patients must have at least one measurable lesion that can be accurately measured with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, or physical exam (by calipers only); (PTCL, AITL and follicular lymphoma patients will be assessed on this study using the Lugano criteria for the evaluation of lymphomas; CTCL and MF patients will be assessed using International Society for Cutaneous Lymphomas [ISCL] and European Organization for Research and Treatment of Cancer [EORTC criteria])

         - 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 are receiving any other investigational agents

         - Patients 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 MEDI-570 or history of anaphylaxis to any biological component

         - 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 active infection by hepatitis B and/or C; for patients with hepatitis B treated with anti-virals to undetectable viral load, and for patients with hepatitis C with undetectable ribonucleic acid (RNA) levels and no evidence of liver damage, enrollment may be considered and should discuss first with study's principal investigator

         - History of human immunodeficiency virus (HIV) infection

         - History of primary immunodeficiency

         - Receipt of live or live attenuated vaccine within 12 weeks prior to enrollment

         - All potential patients must undergo a tuberculosis (TB) test prior to study entry (either purified protein derivative [PPD] or QuantiFERON-TB Gold, whichever is preferred and available at the Institution); patients with a history of TB (even if treated), or evidence of active or latent TB, are excluded; the diagnosis of active TB is defined per current guidelines; patients with a positive TB test (e.g. PPD or QuantiFERON-TB Gold) will be excluded; patients with history of Bacille-Calmette-Guerin (BCG) vaccination will be tested with QuantiFERON-TB Gold test in order to rule out exposure to TB

         - Patients who have undergone allogeneic stem cell transplantation

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

         - Major surgery within 30 days prior or during the study period

         - 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; breastfeeding should be discontinued if the mother is treated with MEDI-570

         - Patients with active, known, or suspected autoimmune disease

             - Participants with well-controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible

             - Participants with the following disease conditions are also eligible:

             - Vitiligo,

             - Type 1 diabetes mellitus

             - Residual hypothyroidism due to autoimmune condition only requiring hormone replacement

             - Euthyroid participants with a history of Grave's disease (participants suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study drug)

             - For patients with ITP (idiopathic thrombocytopenic purpura) or AIHA (autoimmune hemolytic anemia), a case by case discussion with study principal investigator (PI) may be considered

         - Patients with a weight of < 39 kg

At a Glance

National Government IDNCT02520791

IRB#CIRB17-0516

Lead SponsorNational Cancer Institute (NCI)

Lead PhysicianSonali Smith

Collaborator(s)N/A

EligibilityAll
18 Years and up
Recruiting