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

Study 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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03687957
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Washington University School of Medicine
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Milan Chheda, M.D.
Principal Investigator Affiliation Washington University School of Medicine
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioma
Study Website: View Trial Website
Arms & Interventions

Arms

Experimental: Phase I: 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 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

Experimental: 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.

Experimental: 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.

Experimental: 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.

Interventions

Drug: - rhIL-7-hyFc

-Given by intramuscular injection

Drug: - Placebo

-Given by intramuscular injection

Drug: - Temozolomide

-Standard of care

Radiation: - Radiation therapy

-Standard of care

Procedure: - Blood sample

Week 1 (prior to the 1st dose of rhIL-7-hyFc) Week 2 (one week after rhIL-7-hyFc) Week 3 (two weeks after rhIL-7-hyFc) Week 4 (three weeks after rhIL-7-hyFc) Week 13 (prior to the 2nd dose of rhIL-7-hyFc) Week 14 (one week after rhIL-7-hyFc) Week 16 (three weeks after rhIL-7-hyFc) - optional Week 45 (eight weeks after the last dose of rhIL-7-hyFC) If ADA or NADA is observed in week 45, additional blood collections will be required every 2 months in order to monitor ADA/NADA levels until it decreases to the basal level At the time of tumor progression

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mayo Clinic, Rochester, Minnesota

Status

Withdrawn

Address

Mayo Clinic

Rochester, Minnesota, 55905

Washington University School of Medicine, Saint Louis, Missouri

Status

Recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Site Contact

Milan Chheda, M.D.

[email protected]

314-747-2712

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