Any Cancer

EAQ172



Infliximab and Intravenous Immunoglobulin Therapy in Treating Patients with Steroid-Refractory Pneumonitis

STATUS: Closed to Accrual and Intervention


This phase II trial studies how well infliximab and intravenous immunoglobulin therapy work in treating patients with pneumonitis that does not respond to steroid treatment (steroid-refractory). Immunotherapy with monoclonal antibodies such as, infliximab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Intravenous immunoglobulin therapy may improve pneumonitis. It is not yet known whether giving infliximab and intravenous immunoglobulin therapy will work better in treating patients with pneumonitis.
  • Patient must be >= 18 years of age

  • Patients must be English-speaking and have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

  • Patient must be willing and able to undergo arterial blood gas assessment as per the treating investigator. Patient must not have contraindication for arterial blood gas assessment

  • Women must not be pregnant or breast-feeding due to the potential risk to the fetus with infliximab or IVIG. All females of childbearing potential must have a blood test or urine test within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

  • Women of childbearing potential and sexually active males must not conceive or father children by using accepted and effective method(s) of contraception or to abstain from sexual intercourse for a minimum of 56 days (the duration of their participation in the study)

  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3

  • Patient with any solid tumor or hematologic malignancy is eligible * NOTE: Patient may have received any number of lines of prior systemic therapy

  • Patient must have received treatment with an anti-PD-1/PD-L1 agent either alone or in combination with another anti-cancer agent, as their most recent therapy prior to development of pneumonitis * NOTE: Patient may have received anti-PD-1/PD-L1 therapy as standard-of-care or part of a clinical trial

  • Patient must not be receiving anti-PD-1/-PD-L1 agent in combination with any of the following anti-cancer agents: docetaxel, cyclophosphamide, gefitinib, erlotinib, osimertinib, crizotinib, bleomycin, afatinib

  • Patient must have steroid-refractory pneumonitis defined as: * Grade 2 pneumonitis that has not clinically improved by a Common Terminology Criteria for Adverse Events (CTCAE) grade in greater than 72 hours or maximum of 21 days or * Grade 3 or higher pneumonitis that has not clinically improved by a CTCAE grade in greater than 48 hours or maximum of 21 days with high dose corticosteroids (methylprednisolone or prednisone 1-4 mg/kg/equivalent) as their most recent treatment for pneumonitis, as determined by the treating investigator * CTCAE grade 1 radiographic findings

  • Patient must have had pathogen-negative infectious diagnostic evaluation within 21 days prior to randomization, and at a minimum these should include: blood culture, urine culture, sputum culture, and viral panel: rapid flu and RSV (respiratory syncytial virus). Empiric antibiotics for culture negative infections are not an exclusion for study entry

  • Patient must not have clinical evidence of cardiac dysfunction (as determined by the treating investigator) as an alternative diagnosis to steroid-refractory pneumonitis

  • Patient must not be receiving concurrent radiation therapy to the chest

  • Patient must not be deemed to have radiation pneumonitis. Patients with a history of stable radiation pneumonitis not requiring corticosteroid therapy within the last 3 months prior to randomization will be allowed on study

  • Patient must not have pre-existing interstitial lung disease or pneumonitis requiring corticosteroid therapy from any other cause, as determined by the treating investigator

  • Patient must not have an absolute contraindication to IVIG or infliximab, including: clinical history of severe hypersensitivity reaction, selective IgA deficiency, active hepatitis B, active tuberculosis, active human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) where a study subject has a CD4 count of =< 200 at screening, or drug interaction

  • Patient must have a negative tuberculosis assessment (TB spot test, quantiferon gold or tuberculin skin test) within 21 days prior to randomization and either negative or low clinical suspicion

  • Patient must have chest CT scan with or without contrast performed =< 14 days before randomization. Patient must not have a contraindication for CT

United States
IL
Chicago
Northwestern University
Contact: Site Public Contact
Email: cancer@northwestern.edu

MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
Contact: Site Public Contact
Email: jhcccro@jhmi.edu

MI
Battle Creek
Bronson Battle Creek
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Grand Rapids
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Trinity Health Grand Rapids Hospital
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Kalamazoo
West Michigan Cancer Center
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Muskegon
Trinity Health Muskegon Hospital
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Niles
Corewell Health Lakeland Hospitals - Niles Hospital
Contact: Site Public Contact

Norton Shores
Cancer and Hematology Centers of Western Michigan - Norton Shores
Contact: Site Public Contact
Email: connie.szczepanek@crcwm.org

Reed City
Corewell Health Reed City Hospital
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Saint Joseph
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Traverse City
Munson Medical Center
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Wyoming
University of Michigan Health - West
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

NY
New York
Memorial Sloan Kettering Cancer Center
Contact: Site Public Contact

PA
Philadelphia
Fox Chase Cancer Center
Contact: Site Public Contact

VA
Richmond
VCU Massey Cancer Center at Stony Point
Contact: Site Public Contact
Email: ctoclinops@vcu.edu

Virginia Commonwealth University/Massey Cancer Center
Contact: Site Public Contact
Email: CTOclinops@vcu.edu

WI
Chippewa Falls
Marshfield Clinic-Chippewa Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Eau Claire
Marshfield Medical Center-EC Cancer Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Ladysmith
Marshfield Medical Center - Ladysmith
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Marshfield
Marshfield Medical Center-Marshfield
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Minocqua
Marshfield Clinic-Minocqua Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Rice Lake
Marshfield Medical Center-Rice Lake
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Stevens Point
Marshfield Medical Center-River Region at Stevens Point
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Wausau
Marshfield Clinic-Wausau Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Weston
Marshfield Medical Center - Weston
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Wisconsin Rapids
Marshfield Clinic - Wisconsin Rapids Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

PRIMARY OBJECTIVE:
I. To assess pneumonitis response to additional immunosuppression (infliximab or intravenous immunoglobulin therapy [IVIG]) in patients with steroid-refractory pneumonitis at 28-days.

SECONDARY OBJECTIVES:
I. To assess functional parameters of steroid-refractory pneumonitis on days 1, 14, and 28 of receipt of additional immunosuppression (infliximab or IVIG).
II. To assess radiologic parameters of steroid-refractory pneumonitis on days 1, 14, and 28 of receipt of additional immunosuppression (infliximab or IVIG).
III. To assess patient-reported outcomes of steroid-refractory pneumonitis on days 1, 14, and 28 of receipt of additional immunosuppression (infliximab or IVIG).
IV. To assess death in the 28-day period after additional immunosuppression.
V. To assess the rate of infections after additional immunosuppression.

EXPLORATORY OBJECTIVES:
I. To examine serial blood samples in patients who develop steroid-refractory pneumonitis.
II. To evaluate associations between pneumonitis and autoantibodies, T-cell expansion, and baseline cytokines in the blood.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive infliximab intravenously (IV) on day 1 followed by prednisone taper IV or orally (PO) for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician. Patients also undergo computed tomography (CT) and collection of blood samples at screening and on study.

ARM B: Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and collection of blood samples at screening and on study.

After completion of study treatment, patients are followed up at 28, 42 and 56 days.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its NCI Community Oncology Research Program (NCORP).


EAQ172 (Closed)
ECOG-ACRIN Cancer Research Group