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

The Washington University

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Glioma

Treatments: Radiation: Radiation therapy; Drug: Placebo; Drug: rhIL-7-hyFc; Drug: Temozolomide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03687957

201810185

Details and patient eligibility

About

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).

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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42 participants in 9 patient groups

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

Experimental group

Description:

* 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

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

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

Experimental group

Description:

* 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

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

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

Experimental group

Description:

* 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

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

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

Experimental group

Description:

* 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

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

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

Experimental group

Description:

* 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

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

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

Experimental group

Description:

* 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

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

Randomized Phase II: Placebo

Experimental group

Description:

-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.

Treatment:

Drug: Temozolomide

Drug: Placebo

Radiation: Radiation therapy

Randomized Phase II: rhIL-7-hyFc

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy

Phase II Expansion Arm: rhIL-7-hyFc

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: rhIL-7-hyFc

Radiation: Radiation therapy