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

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02520791
First received: August 10, 2015
Last updated: May 23, 2017
Last verified: May 2017
  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 anti-ICOS monoclonal antibody MEDI-570, may block cancer growth in different ways by targeting certain cells.

Condition Intervention Phase
Follicular Variant Peripheral T-Cell Lymphoma Recurrent Angioimmunoblastic T-cell Lymphoma Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma Refractory Angioimmunoblastic T-cell Lymphoma Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Biological: Anti-ICOS Monoclonal Antibody MEDI-570 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of toxicity and safety of MEDI-570, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 weeks after completion of study treatment ]
    Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.

  • Maximum tolerated dose (MTD) of MEDI-570 [ Time Frame: Up to 21 days ]
    Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events, version 4.0.

  • Recommended phase 2 dose of MEDI-570 [ Time Frame: Up to 21 days ]
    Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events, version 4.0.


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: Up to 36 weeks ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.

  • Overall response rate, assessed per the Revised Response Criteria for Malignant Lymphoma of the Lugano Classification [ Time Frame: Up to 36 weeks ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.

  • Overall survival (OS) [ Time Frame: Up to 12 weeks after completion of study treatment ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.

  • Pharmacokinetics (PK), such as plasma concentration and PK parameters, of monoclonal antibody therapy [ Time Frame: Prior to dose on day 1, immediately after dose, and at 6 minutes, 24, 48 and 72 hours post dose of cycle 1 and cycle 2, and then on day 1 pre-dose of every subsequent cycle ]
    Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.

  • Progression-free survival [ Time Frame: Up to 12 weeks after completion of study treatment ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.


Other Outcome Measures:
  • Biomarkers of response and resistance to MEDI-570 [ Time Frame: Up to 36 weeks ]
    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships.


Estimated Enrollment: 46
Actual Study Start Date: April 22, 2016
Estimated Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (MEDI-570)
Patients receive anti-ICOS monoclonal antibody MEDI-570 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.
Biological: Anti-ICOS Monoclonal Antibody MEDI-570
Given IV
Other Name: MEDI-570
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies

Detailed Description:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02520791

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Jasmine M. Zain    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Jasmine M. Zain         
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Joseph M. Tuscano    916-734-3089      
Principal Investigator: Joseph M. Tuscano         
United States, Connecticut
Smilow Cancer Center/Yale-New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Francine M. Foss    203-785-5702      
Principal Investigator: Francine M. Foss         
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Francine M. Foss    203-785-5702      
Principal Investigator: Francine M. Foss         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Julio C. Chavez    800-456-7121    canceranswers@moffitt.org   
Principal Investigator: Julio C. Chavez         
United States, Kentucky
University of Kentucky/Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Hayder Saeed    859-257-3379      
Principal Investigator: Hayder Saeed         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Basem M. William    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Basem M. William         
Canada, Ontario
University Health Network-Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Julio C. Chavez    813-745-4294    julio.c.chavez@moffitt.org   
Principal Investigator: Julio C. Chavez         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Julio Chavez University Health Network Princess Margaret Cancer Center LAO
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02520791     History of Changes
Other Study ID Numbers: NCI-2015-01271
NCI-2015-01271 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PJC-021
9930 ( Other Identifier: University Health Network Princess Margaret Cancer Center LAO )
9930 ( Other Identifier: CTEP )
UM1CA186644 ( US NIH Grant/Contract Award Number )
Study First Received: August 10, 2015
Last Updated: May 23, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 26, 2017