Clinical trial NCT03687957: rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temzolomide
Official title: Effect of rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temzolomide
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: NeoImmuneTech
name: The Foundation for Barnes-Jewish Hospital
First posted: 2018-09-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: -Phase I enrollment will be a sequential enrollment (patients will be stratified by concomitant use of steroids (yes/no). Phase II randomized portion will open with 2 arms being enrolled to in parallel. Phase II expansion cohort will not be randomized.
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Phase I: Safety and tolerability of rhIL-7-hyFc as measured by the maximum tolerated dose (MTD) - Phase I only
timeFrame: Completion of enrollment of phase I portion of study (estimated to be 1 year)
measure: Phase I: Safety and tolerability of rhIL-7-hyFc as measured by dose-limiting toxicities (DLTs)
timeFrame: 30 days from the date when patients receive the 1st dose of rhIL-7-hyFc administration (estimated to be 29 weeks)
measure: Randomized Phase II: Percent increase of absolute lymphocyte count
timeFrame: Prior to adjuvant TMZ (approximately week 4)
measure: Phase II Expansion Cohort: Progression-free survival (PFS)
timeFrame: Through completion of follow-up (estimated to be 5 years and 6 months)
Secondary outcomes:
measure: Phase I and Randomized Phase II: Immunogenicity as measured by anti-drug antibodies
timeFrame: Baseline through Week 14
measure: Phase I: Absolute lymphocyte count (ALC)
timeFrame: 1 year
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Milan Chheda, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.