rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temzolomide

Effect of rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temzolomide

The investigators have developed a phase I/II clinical trial to evaluate the effect of rhIL-7-hyFc on lymphocyte counts in patients with high grade glioma (HGG).

A phase I study will test whether rhIL-7-hyFc can be safely administered to patients with HGG. Six doses of rhIL-7-hyFc will be tested using a mix of Accelerated Phase and standard 3+3 dose-escalation design. The phase II portion to test effect of rhIL-7-hyFc on lymphocyte counts will use placebo-controlled randomization in HGG patients whose treatment include the standard radiation therapy (RT) and temozolomide (TMZ).

Study Overview

• Status: Recruiting
• Conditions: Glioma
• Intervention / Treatment: Drug: rhIL-7-hyFc; Drug: Temozolomide; Radiation: Radiation therapy; Procedure: Blood sample; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Milan Chheda, M.D.; Phone Number: 314-747-2712; Email: mchheda@wustl.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Withdrawn
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Milan Chheda, M.D.; Phone Number: 314-747-2712; Email: mchheda@wustl.edu
      • Sub-Investigator: Richard Hotchkiss, M.D.
      • Sub-Investigator: Sonika Dahiya, M.D.
      • Sub-Investigator: Omar Butt, M.D., Ph.D.
      • Sub-Investigator: John Dipersio, M.D., Ph.D.
      • Principal Investigator: Milan Chheda, M.D.
      • Sub-Investigator: George Ansstas, M.D.
      • Sub-Investigator: Jiayi Huang, M.D.
      • Sub-Investigator: Tanner Johanns, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• World Health Organization (WHO) grade III, grade IV, and high risk grade II gliomas that require RT and TMZ treatment.
• Phase 2 Expansion Cohort ONLY: Must be IDH1 wildtype, as defined by negative immunohistochemistry using an R132H-specific antibody and MGMT promoter unmethylated glioblastoma multiforme (WHO grade IV).
• Post-operative treatment must have included radiation and TMZ. Prior Gliadel Wafers are allowed. Glucocorticoid therapy is allowed. Tumor treating fields (TTF) device is allowed.

• Adequate organ and marrow function defined as follows:

  • Absolute neutrophil count ≥ 1,000/mcL
  • Platelets ≥ 75,000/mcL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤ 3.0 x institutional upper limit of normal
  • AST (SGOT)/ALT (SGPT) ≤ 3.0 × institutional upper limit of normal
  • Absolute lymphocyte count (ALC) ≥ 600/mcL (required for phase I and randomized phase II only)
• Karnofsky Performance Status (KPS) ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).
• Able to provide written informed consent (or consent from a legally authorized representative).

• Women of childbearing potential must have a negative serum pregnancy test prior to study entry (within 14 days). Patients must be willing to be on adequate contraception during treatment.

  • 18 years of age.

Exclusion Criteria:

• Receiving any other investigational agents which may affect patient's lymphocyte counts.
• Pregnant women are excluded from this study because rhIL-7-hyFc has not been evaluated regarding its potential for teratogenic or abortifacients effects. There is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drug, breastfeeding should be discontinued if the mother is treated with rhIL-7-hyFc.
• Has an active viral infection requiring systemic treatment at screening.
• Has active autoimmune disease or syndrome (i.e. moderate or severe rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.,) that requires systemic treatment at the time of screening. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Subjects are permitted to enroll if they have vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), Zoster, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.
• Has clinically significant cardiac enzymes ([Tnl or TnT] or CK-MD)
• Patients with a clinically significant EKG on screening triggering a echocardiogram which is also clinically significant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: rhIL-7-hyFc; Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. rhIL-7hyFc will be given by intramuscular injection starting at the end of RT/TMZ (within 7 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (~Week 37). A total of 4 doses of rhIL-7-hyFc injections are planned; The phase I part will begin with an Accelerated Phase with 1 patient per cohort at the first 2 doses (60 mcg/kg and 120 mcg/kg) followed by a standard 3+3 design on the remaining 4 dose levels	Drug: rhIL-7-hyFc; -Given by intramuscular injection; Drug: Temozolomide; -Standard of care; Other Names: TMZ; Radiation: Radiation therapy; -Standard of care; Other Names: RT; Procedure: Blood sample; Week 1 (prior to the 1st dose of rhIL-7-hyFc); Week 2 (one week after rhIL-7-hyFc); Week 3 (two weeks after rhIL-7-hyFc); Week 4 (three weeks after rhIL-7-hyFc); Week 13 (prior to the 2nd dose of rhIL-7-hyFc); Week 14 (one week after rhIL-7-hyFc); Week 16 (three weeks after rhIL-7-hyFc) - optional; Week 45 (eight weeks after the last dose of rhIL-7-hyFC); If ADA or NADA is observed in week 45, additional blood collections will be required every 2 months in order to monitor ADA/NADA levels until it decreases to the basal level; At the time of tumor progression
Experimental: Randomized Phase II: Placebo; -Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. Placebo will be given by intramuscular injection starting at the end of RT/TMZ (within 14 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (~Week 37). A total of 4 doses of placebo injections are planned.	Drug: Temozolomide; -Standard of care; Other Names: TMZ; Radiation: Radiation therapy; -Standard of care; Other Names: RT; Procedure: Blood sample; Week 1 (prior to the 1st dose of rhIL-7-hyFc); Week 2 (one week after rhIL-7-hyFc); Week 3 (two weeks after rhIL-7-hyFc); Week 4 (three weeks after rhIL-7-hyFc); Week 13 (prior to the 2nd dose of rhIL-7-hyFc); Week 14 (one week after rhIL-7-hyFc); Week 16 (three weeks after rhIL-7-hyFc) - optional; Week 45 (eight weeks after the last dose of rhIL-7-hyFC); If ADA or NADA is observed in week 45, additional blood collections will be required every 2 months in order to monitor ADA/NADA levels until it decreases to the basal level; At the time of tumor progression; Drug: Placebo; -Given by intramuscular injection
Experimental: Randomized Phase II: rhIL-7-hyFc; Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. rhIL-7hyFc will be given by intramuscular injection starting at the end of RT/TMZ (within 14 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (~Week 37). A total of 4 doses of rhIL-7-hyFc injections are planned.	Drug: rhIL-7-hyFc; -Given by intramuscular injection; Drug: Temozolomide; -Standard of care; Other Names: TMZ; Radiation: Radiation therapy; -Standard of care; Other Names: RT; Procedure: Blood sample; Week 1 (prior to the 1st dose of rhIL-7-hyFc); Week 2 (one week after rhIL-7-hyFc); Week 3 (two weeks after rhIL-7-hyFc); Week 4 (three weeks after rhIL-7-hyFc); Week 13 (prior to the 2nd dose of rhIL-7-hyFc); Week 14 (one week after rhIL-7-hyFc); Week 16 (three weeks after rhIL-7-hyFc) - optional; Week 45 (eight weeks after the last dose of rhIL-7-hyFC); If ADA or NADA is observed in week 45, additional blood collections will be required every 2 months in order to monitor ADA/NADA levels until it decreases to the basal level; At the time of tumor progression
Experimental: Phase II Expansion Arm: rhIL-7-hyFc; Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. rhIL-7hyFc will be given by intramuscular injection starting at the end of RT/TMZ (within 14 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (~Week 37). A total of 4 doses of rhIL-7-hyFc injections are planned.	Drug: rhIL-7-hyFc; -Given by intramuscular injection; Drug: Temozolomide; -Standard of care; Other Names: TMZ; Radiation: Radiation therapy; -Standard of care; Other Names: RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Safety and tolerability of rhIL-7-hyFc as measured by the maximum tolerated dose (MTD) - Phase I only	-The maximum tolerated dose (MTD) is defined as the dose level immediately below the non-tolerated dose. A total of at least 6 patients must be treated at a dose level for it to be considered the MTD.	Completion of enrollment of phase I portion of study (estimated to be 1 year)
Phase I: Safety and tolerability of rhIL-7-hyFc as measured by dose-limiting toxicities (DLTs)	-DLT will be defined as ≥ grade 3 non-dermatological and non-hematological AEs that occur within 30 days from the date when patients receive the 1st dose of rhIL-7-hyFc administration and are concluded to be possibly, likely or definitely related to the drug regimen that occurs during cycle 1, with severity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) 5.0.	30 days from the date when patients receive the 1st dose of rhIL-7-hyFc administration (estimated to be 29 weeks)
Randomized Phase II: Percent increase of absolute lymphocyte count		Prior to adjuvant TMZ (approximately week 4)
Phase II Expansion Cohort: Progression-free survival (PFS)	-Defined from date of surgery to date of progression or death due to disease or date of last clinical follow up.	Through completion of follow-up (estimated to be 5 years and 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I and Randomized Phase II: Immunogenicity as measured by anti-drug antibodies	-The formation of anti-drug antibodies (ADA) to rhIL-7-hyFc will be evaluated: BioAgilytix will perform both Elisa Binding (non-neutralizing) and neutralizing antibody assays according to their Standard Operating Procedure.	Baseline through Week 14
Phase I: Absolute lymphocyte count (ALC)		1 year
Phase I and Randomized Phase II: Immunogenicity as measured by neutralizing anti-drug antibodies	-The formation of neutralizing anti-drug antibodies (NADA) to rhIL-7-hyFc will be evaluated: BioAgilytix will perform both Elisa Binding (non-neutralizing) and neutralizing antibody assays according to their Standard Operating Procedure.	Baseline through Week 14

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: The Foundation for Barnes-Jewish Hospital; NeoImmuneTech
• Investigators: Principal Investigator: Milan Chheda, M.D., Washington University School of Medicine

Publications and helpful links

General Publications

• Campian JL, Ghosh S, Kapoor V, Yan R, Thotala S, Jash A, Hu T, Mahadevan A, Rifai K, Page L, Lee BH, Ferrando-Martinez S, Wolfarth AA, Yang SH, Hallahan D, Chheda MG, Thotala D. Long-Acting Recombinant Human Interleukin-7, NT-I7, Increases Cytotoxic CD8 T Cells and Enhances Survival in Mouse Glioma Models. Clin Cancer Res. 2022 Mar 15;28(6):1229-1239. doi: 10.1158/1078-0432.CCR-21-0947.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Estimated): January 31, 2032
• Study Completion (Estimated): January 31, 2032

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 27, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 201810185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No