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

NCT02659800 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: ABTC 1403UM1CA137443IRB00073777
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 10

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-I7 in High Grade Glioma patients with severe lymphopenia, as well as to test the effect of NT-I7 on the CD4 counts of patients in comparison to control participants. This study has both a Phase I and Pilot component.

Conditions

Lymphopenia; Malignant Glioma

Outcome Measures

Primary Outcomes (1)

• Absolute total CD4 cell counts

  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.

  At 6 weeks (after standard radiation and temozolomide treatment completion)

Secondary Outcomes (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 5.0

  4 weeks

Study Arms (5)

Arm A - Low Dexamethasone (LD)

EXPERIMENTAL

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; Biological: NT-I7

Arm B High Dexamethasone (HD)

EXPERIMENTAL

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; Biological: NT-I7

Arm A1 (LD) Control - Placebo

EXPERIMENTAL

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; Biological: NT-I7; Other: Placebo

Arm A2 (LD) MTD

EXPERIMENTAL

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; Biological: NT-I7

Arm B1 HD MTD

EXPERIMENTAL

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; Biological: NT-I7

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A - Low Dexamethasone (LD); Arm A1 (LD) Control - Placebo; Arm A2 (LD) MTD; Arm B High Dexamethasone (HD); Arm B1 HD MTD

NT-I7 BIOLOGICAL

Given IM

Arm A - Low Dexamethasone (LD); Arm A1 (LD) Control - Placebo; Arm A2 (LD) MTD; Arm B High Dexamethasone (HD); Arm B1 HD MTD

Placebo OTHER

Given IM

Arm A1 (LD) Control - Placebo

Eligibility Criteria

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

You may qualify if:

• 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 \>= 1,000/mcL
• Platelets \>= 50,000/mcL (need to confirm before administering study drug)
• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator
• NeoImmuneTech: collaborator

Study Sites (10)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abrams Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Lymphopenia; Glioma

Interventions

efineptakin alfa

Condition Hierarchy (Ancestors)

Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Jian L Campian, MD, PhD

  National Cancer Institute (NCI)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Participant is blinded and partially randomized in the Pilot study.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose Escalation - 3 levels - Group A Dexamethasone less/equal 0.75mg/day; Group B Dexamethasone greater/equal 4mg/day. At MTD Group A - w/outDexamethasone randomized Arm 1 placebo and Arm 2 MTD; Group B MTD w/ Dexamethasone single arm

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 20, 2016
• Study Start: October 30, 2018
• Primary Completion: March 30, 2022
• Study Completion: October 3, 2023
• Last Updated: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)