Advanced Primary Cutaneous T-Cell Non-Hodgkin LymphomaPhase 1NCT02520791

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

A Phase 1 study testing Anti-ICOS Monoclonal Antibody MEDI-570, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Primary Cutaneous T-Cell Non-Hodgkin Lymphoma and Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type, run by National Cancer Institute (NCI) at 23 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type, Recurrent Grade 1 Follicular Lymphoma
What is being tested?: Anti-ICOS Monoclonal Antibody MEDI-570, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 23 sitesin 2 countries
Study dates: 13 Sep 2016to 24 Dec 2026
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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 >= 80 d/L (or >= 8 g/dL)
Patients must not have received a transfusion, with packed red blood cells, within 2 weeks prior to sample being collected
Absolute neutrophil count (ANC) >= 1,500/mcL
Platelets (PLT) >= 50,000/mcL
Absolute CD4 count > 100 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
In patients with bone marrow involvement the minimum requirement is as follows:
Leukocytes >= 2000/mcL
ANC >= 1000/mcL
PLT >= 50 000/mcL
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
The effects of MEDI-570 on the developing human fetus are unknown; for this reason, 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

Who cannot join

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; active viral infection by hepatitis B and hepatitis C could be associated with cytopenias (due to hypersplenism or due to the active virus itself), which could add further risk when a potential immunosuppressive medication is used; 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; the human immunodeficiency virus (HIV) depletes CD4 T-cells and could also have a role in T-cell anergy; since MEDI-570 preferentially affects CD4 T-cell numbers and function, and the resultant immunosuppression by this agent can be prolonged, exposing HIV patients to MEDI-570 will place them in an unnecessary risk of developing infections due to an underlying acquired cellular immunity defect

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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 to rule out active or latent tuberculosis (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 due to the potential toxicity in pre-clinical reproductive studies; in addition, 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
Patients with active, known, or suspected autoimmune disease, except in these conditions:
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 not receiving systemic therapy (i.e., systemic steroids or biologic therapy with disease modifying anti-rheumatic drugs [DMARDs]) within 2 years can be also eligible
Patients with a weight of < 39 kg

Trial locations and contacts

23 sites in 2 countries.

Country

City, postcode or hospital

23 sites in 2 countries

United States21 sites

Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Yale University
New Haven, Connecticut, 06520
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Moffitt Cancer Center
Tampa, Florida, 33612
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467

Other trials in United States

Canada2 sites

University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

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)

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 angioimmunoblastic T-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as anti-ICOS monoclonal antibody MEDI-570, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVE:

To determine the safety, maximum tolerated dose and recommended phase II dose (RP2D) of anti-ICOS monoclonal antibody MEDI-570 (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:

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.

EXPLORATORY OBJECTIVE:

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 21 days for up to 8 cycles 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.

Conditions: Advanced Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3a Follicular Lymphoma, Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
Being tested: Anti-ICOS Monoclonal Antibody MEDI-570, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings: Lymphoma, Follicular, Lymphoma, T-Cell, Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Anti-ICOS Monoclonal Antibody MEDI-570Biological
Also called MEDI-570
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Pharmacological StudyOther
Correlative studies

Study groups in NCT02520791
Study group	Role	What they receive
Treatment (MEDI-570)	Experimental	Patients receive anti-ICOS monoclonal antibody MEDI-570 IV over 1-4 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Receives: Biological: Anti-ICOS Monoclonal Antibody MEDI-570; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of toxicity and safety of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570
Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 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.
Measured: Up to 12 weeks after completion of study treatment
Maximum tolerated dose (MTD) of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570
Toxicity will be assessed using the NCI CTCAE, version 5.0.
Measured: Up to 21 days
Recommended phase 2 dose of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570
Toxicity will be assessed using the NCI CTCAE, version 5.0.
Measured: Up to 21 days

Secondary outcomes (5)

Pharmacokinetics (PK), such as plasma concentration and PK parameters, of monoclonal antibody therapy
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.
Measured: 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
Overall response rate
Assessed per the Revised Response Criteria for Malignant Lymphoma of the Lugano Classification. 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.
Measured: Up to 36 weeks
Progression-free survival
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.
Measured: Up to 12 weeks after completion of study treatment
Immunogenicity
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.
Measured: Up to 36 weeks
Overall survival (OS)
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.
Measured: Up to 12 weeks after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Sep 201624 Dec 2026

First posted13 Aug 2015 (estimated)
Study start13 Sep 2016
Primary completion18 Dec 2024
Study completion24 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced Primary Cutaneous T-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02520791
Sponsor's protocol ID: NCI-2015-01271
Other IDs: NCI-2015-01271, PJC-021, 9930, 9930, UM1CA186644
Status last verified: Jun 2026
First submitted: 10 Aug 2015
Last updated: 26 Jun 2026
Results posted: No
Data monitoring committee: Yes

Publications

Chavez JC, Foss FM, William BM, Brammer JE, Smith SM, Prica A, Zain JM, Tuscano JM, Shah H, Mehta-Shah N, Geethakumari PR, Wang BX, Zantinge S, Wang L, Zhang L, Boutrin A, Zhao W, Cheng L, Standifer N, Hewitt L, Enowtambong E, Shao W, Sharma S, Carlesso G, Moscow JA, Siu LL. Targeting the Inducible T-cell Costimulator (ICOS) in Patients with Relapsed/Refractory T-follicular Helper Phenotype Peripheral T-cell and Angioimmunoblastic T-cell Lymphoma. Clin Cancer Res. 2023 May 15;29(10):1869-1878. doi: 10.1158/1078-0432.CCR-22-2955.
PubMed 36826995