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

NCT03687957 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 201810185
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (4)

• Phase I Only: Safety and Tolerability of rhIL-7-hyFc as Measured by the Maximum Tolerated Dose (MTD) of rhIL-7-hyFc

  -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.

  Within 30 days of treatment start

• Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs)

  -DLTs are defined in the protocol.

  Within 30 days of treatment start

• Randomized Phase II: Percent Change in Absolute Lymphocyte Count (ALC)

  Absolute lymphocyte count (ALC) is a laboratory test that measures the exact number of lymphocytes in a microliter (µL) of blood. Lymphocytes are a type of white blood cell that play a crucial role in the immune system.

  Baseline to Prior to adjuvant TMZ (approximately week 4)

• Phase II Expansion Arm: 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 Outcomes (2)

• Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs)

  Week 1, Week 13, Week 25, and Week 45

• Phase I: Percent Change in Absolute Lymphocyte Count (ALC)

  Baseline to Prior to adjuvant TMZ (approximately week 4)

Study Arms (9)

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

EXPERIMENTAL

* 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; Drug: Temozolomide; Radiation: Radiation therapy

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

EXPERIMENTAL

* 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; Drug: Temozolomide; Radiation: Radiation therapy

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

EXPERIMENTAL

* 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; Drug: Temozolomide; Radiation: Radiation therapy

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

EXPERIMENTAL

* 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; Drug: Temozolomide; Radiation: Radiation therapy

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

EXPERIMENTAL

* 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; Drug: Temozolomide; Radiation: Radiation therapy

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

EXPERIMENTAL

* 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; Drug: Temozolomide; Radiation: Radiation therapy

Randomized Phase II: Placebo

EXPERIMENTAL

-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: Placebo; Drug: Temozolomide; Radiation: Radiation therapy

Randomized Phase II: rhIL-7-hyFc

EXPERIMENTAL

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; Drug: Temozolomide; Radiation: Radiation therapy

Phase II Expansion Arm: rhIL-7-hyFc

EXPERIMENTAL

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; Drug: Temozolomide; Radiation: Radiation therapy

Interventions

rhIL-7-hyFc DRUG

-Given by intramuscular injection

Phase I: rhIL-7-hyFc Dose Level 1 (60 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg); Phase II Expansion Arm: rhIL-7-hyFc; Randomized Phase II: rhIL-7-hyFc

Placebo DRUG

-Given by intramuscular injection

Randomized Phase II: Placebo

Temozolomide DRUG

-Standard of care

Also known as: TMZ

Phase I: rhIL-7-hyFc Dose Level 1 (60 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg); Phase II Expansion Arm: rhIL-7-hyFc; Randomized Phase II: Placebo; Randomized Phase II: rhIL-7-hyFc

Radiation therapy RADIATION

-Standard of care

Also known as: RT

Phase I: rhIL-7-hyFc Dose Level 1 (60 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg); Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg); Phase II Expansion Arm: rhIL-7-hyFc; Randomized Phase II: Placebo; Randomized Phase II: rhIL-7-hyFc

Eligibility Criteria

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

You may qualify if:

• 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.
• years of age.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• NeoImmuneTech: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 35031547 DERIVED

Related Links

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

MeSH Terms

Conditions

Glioma

Interventions

efineptakin alfa; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Limitations and Caveats

After completion of enrollment to the Phase I and Phase II Randomized portions of the trial, funding was depleted. Despite numerous attempts to gain new funding, the Phase II Expansion portion of the trial was never opened to enrollment. The results are late due to this reason.

Results Point of Contact

• Title: Dr. Milan Chheda
• Organization: Washington University School of Medicine

mchheda@wustl.edu

314-747-2712

Study Officials

• Milan Chheda, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Phase II only: This study is triple-blinded (participant, physician, and study coordinator are all blinded; pharmacist and study statistician are not blinded)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: -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.

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 27, 2018
• Study Start: January 4, 2019
• Primary Completion: February 13, 2023
• Study Completion (Estimated): April 13, 2028
• Last Updated: November 25, 2025
• Results First Posted: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)