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

NCT ID: NCT03687957

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-04
• Study Completion Date: 2028-04-13

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).

Conditions

Glioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Phase I: rhIL-7-hyFc Dose Level 1 (60 mcg/kg)

• 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

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg)

• 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

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg)

• 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

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg)

• 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

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg)

• 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

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg)

• 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

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

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.

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

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.

Group Type: EXPERIMENTAL

rhIL-7-hyFc

Intervention Type: DRUG

-Given by intramuscular injection

Temozolomide

Intervention Type: DRUG

-Standard of care

Radiation therapy

Intervention Type: RADIATION

-Standard of care

Interventions

rhIL-7-hyFc

-Given by intramuscular injection

Intervention Type: DRUG

Placebo

-Given by intramuscular injection

Intervention Type: DRUG

Temozolomide

-Standard of care

Intervention Type: DRUG

Radiation therapy

-Standard of care

Intervention Type: RADIATION

Other Intervention Names

TMZ; RT

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NeoImmuneTech

INDUSTRY

Sponsor Role: collaborator

The Foundation for Barnes-Jewish Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Milan Chheda, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35031547 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://siteman.wustl.edu

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

Other Identifiers

201810185

Identifier Type: -

Identifier Source: org_study_id