Brief Title
Study of the Effect NT-I7 on CD4 Counts in Patients With High Grade Gliomas
Official Title
A Phase I and Pilot Study of the Effect of rhIL-7-hyFc (NT-I7) on CD4 Counts in Patients With High Grade Gliomas and Severe Treatment-related CD4 Lymphopenia After Concurrent Radiation and Temozolomide
Brief Summary
The purpose of this study is to determine the maximum tolerated dose (MTD) and select optimal
biological doses (OBD) of the study drug NT-I7 in High Grade Glioma patients with severe
lymphopenia, as well as to test the effect of NT-I7 on the CD4 counts of patients in
comparison to control participants. This study has both a Phase I and Pilot component.
Detailed Description
PRIMARY OBJECTIVES:
Phase I: To determine the MTD (Maximum Tolerated Dose) and select optimal biological doses
(OBD) of NT-I7 in HGG patients with severe lymphopenia
Pilot Study: To test the effect of NT-I7 on CD4 counts compared to control
SECONDARY OBJECTIVES:
1. To evaluate the optimal biological dose of NT-I7
2. To evaluate the effect of concurrent dexamethasone
3. To evaluate the duration of effect on CD4 counts (up to 6 months)
4. To evaluate the total lymphocyte counts over time and serial T cell lymphocyte subtypes
and the effect on T cell repertoire (up to 6 months)
5. To evaluate the serial cytokine levels (up to 6 months)
6. To evaluate the impact of adjuvant temozolomide on NT-I7 effects on CD4 counts
7. To evaluate anti-drug antibodies
8. To evaluate the pharmacokinetic profile of NT-I7 after intramuscular administration in
this patient population
9. To evaluate the safety and toxicity of NT-I7 in patients with high grade glioma
OUTLINE: Patients are assigned to 1 of 2 groups depending on their use of dexamethasone.
GROUP A: Patients not on dexamethasone (or equivalent of an alternative corticosteroid), or
on a dose lower than a physiologic dose (=< 0.75 mg daily)
GROUP B: patients who require dexamethasone (or equivalent of an alternative corticosteroid)
=> 4 mg daily
Patients must have been on the group assignment dose of corticosteroids for at least 5 days
prior to the dose of NT-I7. Corticosteroid dose changes prior to the start of treatment are
allowed as long as they do not alter patient's group assignment.
PHASE I TREATMENT PLAN
All patients (both Groups A and B) will be given a single dose of NT-I7 by intramuscular
injection starting at 60 μg/kg, within one week after completing concurrent RT+TMZ and before
starting adjuvant TMZ treatment, during the standard post-radiation break. Following this
period, as per standard treatment, patients will go on to receive adjuvant temozolomide on
Days 1-5 of 28-day cycles for 6 cycles. There should be about six weeks between the study
injection and the start of adjuvant temozolomide; thus the start of adjuvant TMZ will be
approximately two weeks later than the usual start, which is 4 weeks post-end of radiation.
Patients who are delayed from receiving or are not able to receive adjuvant TMZ treatment may
continue on study; adjuvant TMZ treatment is not a requirement for participation.
PILOT STUDY TREATMENT PLAN
GROUP A: participants will be given either a placebo (NT-I7 diluent) or one dose of NT-I7 at
the Phase I Group A OBD by intramuscular injection within one week after completing
concurrent RT+TMZ and before starting adjuvant TMZ treatment, during the standard
post-radiation break.
GROUP B: participants will be given one dose of NT-I7 at the Phase I Group B OBD by
intramuscular injection within one week after completing concurrent RT+TMZ and before
starting adjuvant TMZ treatment, during the standard post-radiation break.
After completion of study treatment, patients are followed up every 2 months for 2 years and
then every 6 months thereafter.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Absolute total CD4 cell counts
Secondary Outcome
Optimal dose of glycosylated recombinant human interleukin-7 determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Condition
Lymphopenia
Intervention
Laboratory Biomarker Analysis
Study Arms / Comparison Groups
Arm A - Low Dexamethasone (LD)
Description: Patients receive single dose of NT-I7 IM. Treatment continues in the absence of disease progression or unacceptable toxicity. Dose Escalation Laboratory Biomarker Analysis Correlative Studies
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
12
Start Date
October 30, 2018
Completion Date
March 30, 2022
Primary Completion Date
March 30, 2022
Eligibility Criteria
Inclusion Criteria:
- Patients must have histologically confirmed high grade glioma by pathology (World
Health Organization [WHO] grade III and IV)
- Patients' post-operative treatment must have included at least 80% of standard
radiation and concomitant temozolomide; patients may not have received any other
prior chemotherapy, immunotherapy or therapy with biologic agent (including
immunotoxins, immunoconjugates, antisense, peptide receptor antagonists,
interferons, interleukins, tumor infiltrating lymphocytes [TIL],
lymphokine-activated killer [LAK] or gene therapy), or hormonal therapy for their
brain tumor; prior Gliadel wafers are allowed; glucocorticoid therapy is allowed
- Patients must have CD4 =< 300 cells/mm^3 in the last week (7 days) of standard
radiation + temozolomide treatment (58-60 Gy radiation with temozolomide 75 mg/m2
daily during radiation)
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 50,000/mcL (need to confirm before administering study drug)
- Hemoglobin >= 9 g/dL
- Total bilirubin =< institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60
ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT)
=< 1.5 x institutional upper limit of normal
- Patients must have a Karnofsky performance status (KPS) >= 60% (i.e. the patient
must be able to care for himself/herself with occasional help from others)
- Patients must be able to provide written informed consent
- Women of childbearing potential must have a negative serum pregnancy test prior
to study entry; women of childbearing potential and men must agree to use two
birth control methods (either two barrier methods or a barrier method plus a
hormonal method) or abstinence prior to study entry and for the duration of study
participation (through at least 90 days after the last study injection); should a
woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately
- Dexamethasone dose must be provided for treatment group assignment:
- Group A: patients not on dexamethasone or on a dose =< 0.75 mg daily (or
equivalent of an alternative corticosteroid)
- Group B: patients who require dexamethasone >= 4 mg daily (or equivalent of
an alternative corticosteroid) ** Patients must have been on the group
assignment dose of corticosteroids for at least 5 days prior to the dose of
NT-I7; corticosteroid dose changes prior to the start of treatment are
allowed as long as they do not alter patient's group assignment
Exclusion Criteria
- Patients receiving any other investigational agents are ineligible
- Patients with known hypersensitivity to NT-I7 or any component used in the
vehicle/formulation are ineligible
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements, are ineligible
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with NT-I7
- Patients with human immunodeficiency virus (HIV) are excluded
- Patients with a known or screening-period-determined corrected QT (QTc) interval > 450
msec and patients who require a therapy with a drug known to prolong the QT/QTc
interval, are ineligible
- Patients with a history of or who currently have evidence of autoimmune disease (other
than autoimmune thyroid disease managed with thyroid hormone replacement or vitiligo)
including: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus,
multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune
hepatitis, Wegener's etc., are ineligible
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jian L Campian, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02659800
Organization ID
ABTC 1403
Secondary IDs
UM1CA137443
Responsible Party
Sponsor
Study Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Jian L Campian, MD, PhD, Study Chair, National Cancer Institute (NCI)
Verification Date
May 2022