Glioma
Conditions
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).
Interventions
DRUGrhIL-7-hyFc
-Given by intramuscular injection
DRUGPlacebo
-Given by intramuscular injection
DRUGTemozolomide
-Standard of care
RADIATIONRadiation therapy
-Standard of care
Sponsors
NeoImmuneTech
The Foundation for Barnes-Jewish Hospital
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Phase II only: This study is triple-blinded (participant, physician, and study coordinator are all blinded; pharmacist and study statistician are not blinded)
Intervention model description
-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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Only: Safety and Tolerability of rhIL-7-hyFc as Measured by the Maximum Tolerated Dose (MTD) of rhIL-7-hyFc | Within 30 days of treatment start | -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. |
| Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | Within 30 days of treatment start | -DLTs are defined in the protocol. |
| Randomized Phase II: Percent Change in Absolute Lymphocyte Count (ALC) | Baseline to Prior to adjuvant TMZ (approximately week 4) | 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. |
| Phase II Expansion Arm: Progression-free Survival (PFS) | Through completion of follow-up (estimated to be 5 years and 6 months) | -Defined from date of surgery to date of progression or death due to disease or date of last clinical follow up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1, Week 13, Week 25, and Week 45 | * 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. The data will be presented if anti-drug antibodies are detected or not detected in the samples. * Week 1 will be prior to injection of 1st dose of rhIL-7-hyFc, week 13 will be prior to the 2nd dose of rhIL-7-hyFc, and week 45 will be 8 weeks after the last dose of rhIL-7-hyFc. |
| Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | Baseline to Prior to adjuvant TMZ (approximately week 4) | 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. |
Countries
United States
Participant flow
Recruitment details
The Phase II Expansion Arm never opened to enrollment and no participants were enrolled in this portion of the trial.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 1 |
| 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 | 1 |
| 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 | 3 |
| 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 | 6 |
| 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 | 6 |
| 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 | 2 |
| 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. | 11 |
| 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. | 11 |
| Randomized Phase II: Not Randomized Enrolled to Randomized Phase II trial portion but not randomized. | 1 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 3 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Disease progression | 0 | 1 | 1 | 2 | 2 | 0 | 2 | 1 | 0 | 0 |
| Overall Study | New malignancy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Patient went on hospice | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 0 | 3 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase I: rhIL-7-hyFc Dose Level 1 (60 mcg/kg) | Total | Randomized Phase II: Not Randomized | Randomized Phase II: rhIL-7-hyFc | Randomized Phase II: Placebo | Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57 years | 57.5 years | 42 years | 61 years | 58 years | 34 years | 57.5 years | 63 years | 46 years | 32 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 41 Participants | 1 Participants | 11 Participants | 11 Participants | 2 Participants | 5 Participants | 6 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 39 Participants | 1 Participants | 9 Participants | 10 Participants | 2 Participants | 6 Participants | 6 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 42 participants | 1 participants | 11 participants | 11 participants | 2 participants | 6 participants | 6 participants | 3 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 15 Participants | 1 Participants | 4 Participants | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 27 Participants | 0 Participants | 7 Participants | 6 Participants | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 1 / 3 | 5 / 6 | 5 / 6 | 2 / 2 | 9 / 11 | 10 / 11 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 5 / 6 | 6 / 6 | 2 / 2 | 9 / 11 | 11 / 11 | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 | 1 / 1 | 0 / 3 | 2 / 6 | 4 / 6 | 1 / 2 | 3 / 11 | 4 / 11 | 0 / 1 |
Outcome results
Primary
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.
Time frame: Through completion of follow-up (estimated to be 5 years and 6 months)
Population: The Phase II Expansion Arm of the trial never opened to enrollment and no participants were enrolled.
Primary
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.
Time frame: Within 30 days of treatment start
Population: All Phase I participants are evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I Only: Safety and Tolerability of rhIL-7-hyFc as Measured by the Maximum Tolerated Dose (MTD) of rhIL-7-hyFc | 720 mcg/kg |
Primary
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.
Time frame: Within 30 days of treatment start
Population: This outcome measure is for Phase I participants only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I: Safety and Tolerability of rhIL-7-hyFc as Measured by Number of Participants With Dose-limiting Toxicities (DLTs) | 2 Participants |
Primary
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.
Time frame: Baseline to Prior to adjuvant TMZ (approximately week 4)
Population: Only participants in the Randomized Phase II Placebo and Randomized Phase II rhIL-7-hyFc are evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Randomized Phase II: Placebo | Randomized Phase II: Percent Change in Absolute Lymphocyte Count (ALC) | 16.66667 percent change | Standard Deviation 28.36597 |
| Randomized Phase II: rhIL-7-hyFc | Randomized Phase II: Percent Change in Absolute Lymphocyte Count (ALC) | 147.8261 percent change | Standard Deviation 285.9597 |
Secondary
Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs)
* 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. The data will be presented if anti-drug antibodies are detected or not detected in the samples. * Week 1 will be prior to injection of 1st dose of rhIL-7-hyFc, week 13 will be prior to the 2nd dose of rhIL-7-hyFc, and week 45 will be 8 weeks after the last dose of rhIL-7-hyFc.
Time frame: Week 1, Week 13, Week 25, and Week 45
Population: Samples were not collected at all time points if a participant was removed from treatment or removed from the study prior to that timepoint. Week 25 was removed with amendment #4 and only one participant had a sample collected at this time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 1 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 1 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 1 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 1 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 1 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 1 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 1 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 2 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 3 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 2 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 6 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 2 Participants |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 5 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 5 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 1 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 1 Participants |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 2 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 0 Participants |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 0 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 6 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 2 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 9 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 1 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 4 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Randomized Phase II: Placebo | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 0 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Detected | 0 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Detected | 7 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 25 | Not Detected | 0 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Not Detected | 10 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Detected | 5 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 1 | Detected | 1 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 45 | Not Detected | 0 Participants |
| Randomized Phase II: rhIL-7-hyFc | Phase I and Randomized Phase II: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) | Week 13 | Not Detected | 0 Participants |
Secondary
Phase I: 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.
Time frame: Baseline to Prior to adjuvant TMZ (approximately week 4)
Population: Only Phase I participants are evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: rhIL-7-hyFc All Dose Levels | Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | 37.5 percent change | — |
| Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) | Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | -22.222 percent change | — |
| Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) | Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | 25 percent change | Standard Deviation 161.231 |
| Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) | Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | 129.545 percent change | Standard Deviation 81.696 |
| Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) | Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | 52.083 percent change | Standard Deviation 87.525 |
| Phase I: rhIL-7-hyFc Dose Level 6 (960 mcg/kg) | Phase I: Percent Change in Absolute Lymphocyte Count (ALC) | -5.639 percent change | Standard Deviation 88.787 |