Clinical Trials /

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

NCT03687957

Description:

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).

Related Conditions:
  • Malignant Glioma
  • WHO Grade II Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 201810185
  • NCT ID: NCT03687957

Conditions

  • Glioma

Interventions

DrugSynonymsArms
rhIL-7-hyFcPhase I: rhIL-7-hyFc
PlaceboPhase II: Placebo
TemozolomideTMZPhase I: rhIL-7-hyFc

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Phase I: rhIL-7-hyFcExperimentalPer 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 5 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
  • rhIL-7-hyFc
  • Temozolomide
Phase II: PlaceboExperimental-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 5 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.
  • Placebo
  • Temozolomide
Phase II: rhIL-7-hyFcExperimentalPer 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 5 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.
  • rhIL-7-hyFc
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          -  World Health Organization (WHO) grade III, grade IV, and high risk grade II gliomas
             that require RT and TMZ treatment.

          -  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

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I portion: Safety and tolerability of rhIL-7-hyFc as measured by the maximum tolerated dose (MTD) - Phase I only
Time Frame:Completion of enrollment of phase I portion of study (estimated to be 1 year)
Safety Issue:
Description:-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.

Secondary Outcome Measures

Measure:Immunogenicity as measured by anti-drug antibodies
Time Frame:Baseline through Week 14
Safety Issue:
Description:-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.
Measure:Phase I portion: Absolute lymphocyte count (ALC)
Time Frame:1 year
Safety Issue:
Description:
Measure:Immunogenicity as measured by neutralizing anti-drug antibodies
Time Frame:Baseline through Week 14
Safety Issue:
Description:-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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

June 5, 2020