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IL-7 in Increasing Low CD4 Counts After Concurrent Radiation and Temozolomide Treatment in Patients With High Grade Gliomas

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ClinicalTrials.gov Identifier: NCT02659800
Recruitment Status : Suspended (Drug expired, waiting on stability testing)
First Posted : January 20, 2016
Last Update Posted : May 17, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Revimmune
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
This pilot, partially randomized clinical trial studies how well glycosylated recombinant human interleukin-7 works in increasing low cluster of differentiation (CD)4 counts after concurrent radiation and temozolomide treatment in patients with gliomas that tend to grow rapidly and spread (high-grade). Treatment with radiation and chemotherapy, such as temozolomide, may cause an abnormal decrease in CD4 cells, which are an important part of the immune system. Glycosylated recombinant human interleukin-7 may increase CD4 cell counts and improve survival.

Condition or disease Intervention/treatment Phase
Lymphopenia Malignant Glioma Other: Laboratory Biomarker Analysis Biological: Glycosylated Recombinant Human Interleukin-7 Other: Placebo Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Supportive Care
Official Title: The Effect of IL-7 (CYT107) on CD4 Counts in Patients With High Grade Gliomas and Severe Treatment-Related CD4 Lymphopenia After Concurrent Radiation and Temozolomide
Estimated Study Start Date : December 15, 2018
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : August 15, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Arm A1 (placebo)

Patients receive placebo IM once weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given IV

Experimental: Arm A2 (CYT107 at 10 ug/kg)

Patients receive glycosylated recombinant human interleukin-7 at 10 ug/kg IM once weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Glycosylated Recombinant Human Interleukin-7
Given IV
Other Name: CYT107

Experimental: Arm A3 (CYT107 at 20 ug/kg)

Patients receive glycosylated recombinant human interleukin-7 at 20 ug/kg IM once weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Glycosylated Recombinant Human Interleukin-7
Given IV
Other Name: CYT107

Experimental: Arm B1 (CYT107 at 10 ug/kg)

Patients receive glycosylated recombinant human interleukin-7 as in Arm A2. Patients also on Dexamethasone >0.75mg daily

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Glycosylated Recombinant Human Interleukin-7
Given IV
Other Name: CYT107

Experimental: Arm B2 (CYT107 at 20 ug/kg)

Patients receive glycosylated recombinant human interleukin-7 as in Arm A3. Patients also on Dexamethasone >0.75mg daily

Laboratory Biomarker Analysis Correlative Studies

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Glycosylated Recombinant Human Interleukin-7
Given IV
Other Name: CYT107




Primary Outcome Measures :
  1. Absolute total CD4 cell counts [ Time Frame: At 6 weeks (after standard radiation and temozolomide treatment completion) ]
    The primary treatment effect is defined as an absolute increase in CD4 counts in patients treated with glycosylated recombinant human interleukin-7 compared to the control group patients without glycosylated recombinant human interleukin-7 at week 6 after radiation treatment + temozolomide treatment.


Secondary Outcome Measures :
  1. 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 4.0 [ Time Frame: 4 weeks ]
    The optimal dose will be selected based on the highest absolute increase of CD4 counts compared to the control if toxicity profiles are similar between the two dose levels. Otherwise, safety will be the first consideration for dose selection. The results of the two concurrent dexamethasone groups will be summarized with standard descriptive statistics. The dose selection criteria will be similar to the non-dexamethasone groups with priority on safety rather than the highest absolute increase of CD4 counts.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 =< 200 cells/mm^3 in the last week (7 days) of standard radiation + temozolomide treatment
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • 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 30 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
    • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
    • Dexamethasone dose must be provided for treatment stratification:

      • Group A: patients not on dexamethasone or on a dose =< 0.75mg daily (or equivalent of an alternative corticosteroid)
      • Group B: patients who require dexamethasone > 0.75mg daily (or equivalent of an alternative corticosteroid) ** 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 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 =< 200 cells/mm^3 in the last week (7 days) of standard radiation + temozolomide treatment
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • 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 30 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
    • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
    • Dexamethasone dose must be provided for treatment stratification:

      • Group A: patients not on dexamethasone or on a dose =< 0.75mg daily (or equivalent of an alternative corticosteroid)
      • Group B: patients who require dexamethasone > 0.75mg daily (or equivalent of an alternative corticosteroid) ** 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 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 CYT107
  • Patients with human immunodeficiency virus (HIV) are excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659800


Locations
United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3410
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095
United States, Maryland
Johns Hopkins Oncology Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Abrams Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Revimmune
Investigators
Study Chair: Jian L Campian, MD, PhD National Cancer Institute (NCI)

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02659800     History of Changes
Other Study ID Numbers: ABTC 1403
UM1CA137443 ( U.S. NIH Grant/Contract )
IRB00073777 ( Other Identifier: JHMIRB )
First Posted: January 20, 2016    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioma
Lymphopenia
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents