ACTIVE_NOT_RECRUITING

Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to CAR-T Cell Therapy

Conditions

Cytokine Release Syndrome ICANS Lymphoma, Non-Hodgkin Multiple Myeloma Acute Lymphoblastic Leukemia Siltuximab Chimeric Antigen Receptor T-cell Therapy Immune effector Cell associated Neurotoxicity Syndrome Lymphoma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study will evaluate the use of siltuximab to decrease the severity of cytokine release syndrome (CRS) and immune effector cell-associated neurological syndrome (ICANS) in patients who will receive chimeric antigen receptor (CAR) T-cell therapy for the treatment of hematological malignancies.

Official Title

A Phase II Pilot Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to Chimeric Antigen Receptor T-Cell Therapy (CAR-T) in Hematological Malignancies

Quick Facts

Study Start:2021-11-15

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04975555

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients who are planned to receive chimeric antigen receptor T-cell therapy as per the United States Food and Drug Agency (USFDA) approved indications for Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma (MCL), Follicular lymphoma (FL), Primary mediastinal large B-cell lymphoma (PMBCL), High grade B-cell lymphoma, DLBCL arising from follicular lymphoma, Multiple myeloma and B-cell precursor acute lymphoblastic leukemia * Patients with hepatitis C virus (HCV) can be included if they have completed therapy for hepatitis C with undetectable HCV RNA viral load. * Patients with Hepatitis B can be included if they are on suppressive therapy for hepatitis B infection and with no detectable viral load. * Adequate organ function as defined below unless attributed to disease involvement.Acceptable window for assessing adequate organ function is 7 days to 30 days before planned CAR T-cell infusion with day 0 as the planned day of CAR T-cell infusion.Adequate liver function (bilirubin \< 2mg/dL, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<3 x ULN), adequate kidney function (crcl \> 30ml/min using Cockcroft-Gault, based on actual weight) and adequate hematological parameters (Absolute neutrophil count ≥ 1,000/µL, Hemoglobin \> 8, Platelet Count ≥ 50,000/ µL) * Patients able to tolerate washout periods for therapies prior to CAR T-cell infusion. Systemic therapy: Washout period is 2 weeks prior to CAR T-cell infusion. Radiation therapy: Washout period is 1 week prior to CAR T-cell infusion. Corticosteroids: The washout period is 5 days prior to CAR T-cell infusion. * A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial. * For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 months after infusion of siltuximab. * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner * Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of the investigational product and being admitted, when required, for at least 24 hours during investigational product administration.	* Subjects requiring ongoing daily corticosteroid therapy at a dose of \> 10 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable. * Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the principal investigator (PI) * Pregnant women are excluded from this study. * Evidence of ongoing systemic bacterial, or fungal or viral infection, except localized fungal infection of skin or nails. * Patients with ongoing or past HIV infection.

Inclusion Criteria

Exclusion Criteria

* Patients who are planned to receive chimeric antigen receptor T-cell therapy as per the United States Food and Drug Agency (USFDA) approved indications for Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma (MCL), Follicular lymphoma (FL), Primary mediastinal large B-cell lymphoma (PMBCL), High grade B-cell lymphoma, DLBCL arising from follicular lymphoma, Multiple myeloma and B-cell precursor acute lymphoblastic leukemia
* Patients with hepatitis C virus (HCV) can be included if they have completed therapy for hepatitis C with undetectable HCV RNA viral load.
* Patients with Hepatitis B can be included if they are on suppressive therapy for hepatitis B infection and with no detectable viral load.
* Adequate organ function as defined below unless attributed to disease involvement.Acceptable window for assessing adequate organ function is 7 days to 30 days before planned CAR T-cell infusion with day 0 as the planned day of CAR T-cell infusion.Adequate liver function (bilirubin \< 2mg/dL, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<3 x ULN), adequate kidney function (crcl \> 30ml/min using Cockcroft-Gault, based on actual weight) and adequate hematological parameters (Absolute neutrophil count ≥ 1,000/µL, Hemoglobin \> 8, Platelet Count ≥ 50,000/ µL)
* Patients able to tolerate washout periods for therapies prior to CAR T-cell infusion. Systemic therapy: Washout period is 2 weeks prior to CAR T-cell infusion. Radiation therapy: Washout period is 1 week prior to CAR T-cell infusion. Corticosteroids: The washout period is 5 days prior to CAR T-cell infusion.
* A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
* For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 months after infusion of siltuximab.
* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
* Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of the investigational product and being admitted, when required, for at least 24 hours during investigational product administration.

* Subjects requiring ongoing daily corticosteroid therapy at a dose of \> 10 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable.
* Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the principal investigator (PI)
* Pregnant women are excluded from this study.
* Evidence of ongoing systemic bacterial, or fungal or viral infection, except localized fungal infection of skin or nails.
* Patients with ongoing or past HIV infection.

Contacts and Locations

Principal Investigator

Amitkumar Mehta, MD

PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35294

United States

Collaborators and Investigators

Sponsor: University of Alabama at Birmingham

Amitkumar Mehta, MD, PRINCIPAL_INVESTIGATOR, University of Alabama at Birmingham

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-11-15

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2021-11-15

Study Completion Date2027-12-31

Terms related to this study

Keywords Provided by Researchers

Siltuximab
Chimeric Antigen Receptor T-cell Therapy
Cytokine release syndrome
Immune effector Cell associated Neurotoxicity Syndrome
Lymphoma
Multiple Myeloma
Acute lymphoblastic Leukemia

Additional Relevant MeSH Terms

Cytokine Release Syndrome
ICANS
Lymphoma, Non-Hodgkin
Multiple Myeloma
Acute Lymphoblastic Leukemia