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

NCT02520791 | Active Not Recruiting Phase 1 DMC

• 4 other identifiers: NCI-2015-01271PJC-0219930UM1CA186644
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 23

Brief Summary

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.

Conditions

Recurrent Grade 3a Follicular Lymphoma; Recurrent Mycosis Fungoides; Refractory Grade 1 Follicular Lymphoma; Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type; Refractory Grade 2 Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Refractory Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type; Advanced Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Grade 3a Follicular Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Stage II Mycosis Fungoides AJCC v7; Stage IV Mycosis Fungoides AJCC v7

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 21 days

Secondary Outcomes (5)

• Pharmacokinetics (PK), such as plasma concentration and PK parameters, of monoclonal antibody therapy

  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

  Up to 36 weeks

• Progression-free survival

  Up to 12 weeks after completion of study treatment

• Immunogenicity

  Up to 36 weeks

• Overall survival (OS)

  Up to 12 weeks after completion of study treatment

Other Outcomes (1)

• Biomarkers of response and resistance to anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570

  Up to 36 weeks

Study Arms (1)

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.

Biological: Anti-ICOS Monoclonal Antibody MEDI-570; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Anti-ICOS Monoclonal Antibody MEDI-570 BIOLOGICAL

Given IV

Also known as: MEDI-570

Treatment (MEDI-570)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (MEDI-570)

Pharmacological Study OTHER

Correlative studies

Treatment (MEDI-570)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \>= 80 d/L (or \>= 8 g/dL)

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (23)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• 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.

  PMID: 36826995 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, T-Cell; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous

Interventions

MEDI-570

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Julio C Chavez

  University Health Network Princess Margaret Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2015
• First Posted: August 13, 2015
• Study Start: September 13, 2016
• Primary Completion: December 18, 2024
• Study Completion (Estimated): December 24, 2026
• Last Updated: April 13, 2026

Record last verified: 2025-12

Locations

CA (2); US (21)