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Study of the Effect IL 7/ NT-I7 on CD4 Counts in Patients With High Grade Gliomas

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ClinicalTrials.gov Identifier: NCT02659800
Recruitment Status : Recruiting
First Posted : January 20, 2016
Last Update Posted : December 19, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Matthew Larson Foundation
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
The purpose of this study is to determine the maximum tolerated dose (MTD) and select optimal biological doses (OBD) of the study drug NT-17 in High Grade Glioma patients with severe lymphopenia, as well as to test the effect of NT-17 on the CDR counts of patients in comparison to control participants. This study has both a Phase I and Pilot component.

Condition or disease Intervention/treatment Phase
Lymphopenia Malignant Glioma Other: Laboratory Biomarker Analysis Biological: NT-I7 Other: Placebo Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Dose Escalation - 3 levels - Group A Dexamethasone less/equal 0.75mg/day; Group B Dexamethasone greater/equal 4mg/day. At MTD Group A - w/Dexamethasone randomized Arm 1 placebo and Arm 2 MTD; Group B MTD w/out Dexamethasone single arm
Masking: Double (Participant, Care Provider)
Masking Description: participant is blinded and randomized in the second part of study.
Primary Purpose: Supportive Care
Official Title: A Phase I and Pilot Study of the Effect of rhIL-7-hyFc (NT-I7) on CD4 Counts in Patients With High Grade Gliomas and Severe Treatment-related CD4 Lymphopenia After Concurrent Radiation and Temozolomide
Actual Study Start Date : October 30, 2018
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : August 15, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A - Low Dexamethasone (LD)

Patients receive single dose of NT-I7 IM. Treatment continues in the absence of disease progression or unacceptable toxicity. Dose Escalation

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: NT-I7
Given IM

Experimental: Arm B High Dexamethasone (HD)

Patients receive single dose of NT-I7 IM. Treatment continues in the absence of disease progression or unacceptable toxicity. Dose Escalation

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: NT-I7
Given IM

Experimental: Arm A1 (LD) Control - Placebo

Patients receive single dose Placebo IM (blinded). Patients also on Dexamethasone </=0.75mg daily Treatment continues in the absence of disease progression or unacceptable toxicity. Pilot

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: NT-I7
Given IM

Other: Placebo
Given IM

Experimental: Arm A2 (LD) MTD

Patients receive single dose MTD NT-I7 IM determined in Arm A (Blinded) . Patients also on Dexamethasone </=0.75mg daily Treatment continues in the absence of disease progression or unacceptable toxicity. Pilot

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: NT-I7
Given IM

Experimental: Arm B1 HD MTD

Patients receive single dose MTD NT-I7 IM determined in Arm B (Blinded) . Patients also on Dexamethasone >/= 4mg daily Treatment continues in the absence of disease progression or unacceptable toxicity. Pilot

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: NT-I7
Given IM




Primary Outcome Measures :
  1. Absolute total CD4 cell counts [ Time Frame: At 6 weeks (after standard radiation and temozolomide treatment completion) ]
    The primary treatment effect is defined as an absolute increase in CD4 counts in patients treated with glycosylated recombinant human interleukin-7 compared to the control group patients without glycosylated recombinant human interleukin-7 at week 6 after radiation treatment + temozolomide treatment.


Secondary Outcome Measures :
  1. Optimal dose of glycosylated recombinant human interleukin-7 determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: 4 weeks ]
    The optimal dose will be selected based on the highest absolute increase of CD4 counts compared to the control if toxicity profiles are similar between the two dose levels. Otherwise, safety will be the first consideration for dose selection. The results of the two concurrent dexamethasone groups will be summarized with standard descriptive statistics. The dose selection criteria will be similar to the non-dexamethasone groups with priority on safety rather than the highest absolute increase of CD4 counts.



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

Inclusion Criteria:

  • Patients must have histologically confirmed high grade glioma by pathology (World Health Organization [WHO] grade III and IV)

    • Patients' post-operative treatment must have included at least 80% of standard radiation and concomitant temozolomide; patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes [TIL], lymphokine-activated killer [LAK] or gene therapy), or hormonal therapy for their brain tumor; prior Gliadel wafers are allowed; glucocorticoid therapy is allowed
    • Patients must have CD4 =< 300 cells/mm^3 in the last week (7 days) of standard radiation + temozolomide treatment (58-60 Gy radiation with temozolomide 75 mg/m2 daily during radiation)
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • Hemoglobin >= 9 g/dL
    • Total bilirubin =< institutional upper limit of normal
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
    • Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
    • Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
    • Patients must have a Karnofsky performance status (KPS) >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
    • Patients must be able to provide written informed consent
    • Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use two birth control methods (either two barrier methods or a barrier method plus a hormonal method) or abstinence prior to study entry and for the duration of study participation (through at least 90 days after the last study injection); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
    • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
    • Dexamethasone dose must be provided for treatment group assignment:

      • Group A: patients not on dexamethasone or on a dose =< 0.75 mg daily (or equivalent of an alternative corticosteroid)
      • Group B: patients who require dexamethasone >= 4 mg daily (or equivalent of an alternative corticosteroid) ** Patients must have been on the group assignment dose of corticosteroids for at least 5 days prior to the dose of NT-I7; corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patient's group assignment

Exclusion Criteria

  • Patients receiving any other investigational agents are ineligible
  • Patients with known hypersensitivity to NT-I7 or any component used in the vehicle/formulation are ineligible
  • Patients with 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, are ineligible
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with NT-I7
  • Patients with human immunodeficiency virus (HIV) are excluded
  • Patients with a known or screening-period-determined corrected QT (QTc) interval > 450 msec and patients who require a therapy with a drug known to prolong the QT/QTc interval, are ineligible
  • Patients with a history of or who currently have evidence of autoimmune disease (other than autoimmune thyroid disease managed with thyroid hormone replacement or vitiligo) including: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc., are ineligible

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659800


Contacts
Contact: Stuart A Grossman, MD 410-955-8837 jfisher@jhmi.edu
Contact: Joy D Fisher, MA 410-955-3657 jfisher@jhmi.edu

Locations
United States, Alabama
UAB Comprehensive Cancer Center Not yet recruiting
Birmingham, Alabama, United States, 35294-3410
Contact: Thiru Pillay, RN    205-934-1842    thiru@uab.edu   
Principal Investigator: Burt Nabors, MD         
United States, California
Jonsson Comprehensive Cancer Center at UCLA Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Timothy Cloughesy, MD    310-825-5321    TCloughesy@mednet.ucla.edu   
Principal Investigator: Timothy Cloughesy, MD         
UCSF Comprehensive Cancer Center Withdrawn
San Francisco, California, United States, 94115
United States, Maryland
Johns Hopkins Oncology Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Michaella Iacoboni, RN    410-955-4009    msheeh13@jhmi.edu   
Principal Investigator: Stuart A Grossman, MD         
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Jennifer Barrs    617-632-6119    JenniferA_Barrs@DFCI.HARVARD.EDU   
Principal Investigator: Patrick Wen, MD         
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital Not yet recruiting
Detroit, Michigan, United States, 48202
Contact: Amy Williamson, RN       awillia12@hfhs.org   
Contact: Emily Krozek, MHSA       Ekrozek1@hfhs.org   
Principal Investigator: Tobias Walbert, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jian L Campian, MD    314-747-4241      
Principal Investigator: Jian Campian, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10021
Contact: Thomas Kaley, MD    212-639-5122      
Principal Investigator: Thomas Kaley, MD         
United States, North Carolina
Wake Forest University Comprehensive Cancer Center Not yet recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University CCC    336-713-6771      
Principal Investigator: Glenn Lesser, MD         
United States, Ohio
Cleveland Clinic Taussig Cancer Center Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Cancer Center-Cares    216-444-7923      
Principal Investigator: David Peereboom, MD         
Sub-Investigator: Manmeet Ahluwalia, MD         
United States, Pennsylvania
Abrams Cancer Center of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Clinical Trials Office-Abrams Cancer Center    800-474-9892      
Principal Investigator: Arati Desai, MD         
Hillman Cancer Center at University of Pittsburgh Cancer Institute Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Rita Johnson, RN       johnsonr1@msx.upmc.edu   
Principal Investigator: Frank Lieberman, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Matthew Larson Foundation
Investigators
Study Chair: Jian L Campian, MD, PhD National Cancer Institute (NCI)

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02659800     History of Changes
Other Study ID Numbers: ABTC 1403
UM1CA137443 ( U.S. NIH Grant/Contract )
IRB00073777 ( Other Identifier: JHMIRB )
118924 ( Other Grant/Funding Number: Matthew Larson Foundation )
First Posted: January 20, 2016    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioma
Lymphopenia
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Dexamethasone acetate
Dexamethasone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors