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
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|ClinicalTrials.gov Identifier: NCT04975555|
Recruitment Status : Recruiting
First Posted : July 23, 2021
Last Update Posted : December 20, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Cytokine Release Syndrome ICANS Lymphoma, Non-Hodgkin Multiple Myeloma Acute Lymphoblastic Leukemia||Drug: Siltuximab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||November 15, 2021|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2025|
Patients who experience CRS/ICANS will receive this treatment
Siltuximab is administered at the dose of 11mg/kg via intravenous infusion over 1 hour. If no resolution of CRS is achieved then a repeat dose of siltuximab at the dose of 11mg/kg via intravenous infusion over 1 hour will be given.
- Participants with a complete response for cytokine release syndrome (CRS) [ Time Frame: Baseline through 14 days ]Participants who achieve a resolution of CRS. Resolution of CRS is defined as absence of symptoms leading to diagnosis of CRS for 24 hours.
- Participants with a response for Immune effector Cell Associated Neurotoxicity Syndrome (ICANS) [ Time Frame: Baseline through 28 days ]Participants who achieve a resolution or improvement in their ICANS. Complete response or partial response for ICANS is defined as either complete disappearance or decrease in the grade of severity as measured by ASTCT Consensus Grading for ICANS. The ASTCT grade is from 1 to 5 for ICANS with 1 being mild symptoms and 5 being severe symptoms.
- Participants experiencing adverse events from Siltuximab [ Time Frame: Baseline through 28 days ]All Adverse Events (AE's) will be reported and evaluated using National Cancer Institute's Common Terminology Criteria (CTCAE) v5.0.
- Participants with response to CAR T-cell therapy [ Time Frame: Baseline through day 90 ]This will be measured by using specific criteria's for Lymphoma, Multiple Myeloma or Acute Lymphoblastic Leukemia (ALL) [Based on the patients diagnosis]
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
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): NCT04975555
|Contact: Mayur Narkhedefirstname.lastname@example.org|
|United States, Alabama|
|University of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator: Mayur S Narkhede, M.D|
|Sub-Investigator: Amitkumar Mehta, M.D|
|Sub-Investigator: Gaurav Goyal, M.D|
|Sub-Investigator: Susan Bal, M.D|
|Sub-Investigator: Pankit Vachhani, M.D|
|Sub-Investigator: Smith Giri, M.D|
|Principal Investigator:||Mayur S Narkhede||University of Alabama at Birmingham|
|Responsible Party:||Mayur Narkhede, Assistant Professor, University of Alabama at Birmingham|
|Other Study ID Numbers:||
|First Posted:||July 23, 2021 Key Record Dates|
|Last Update Posted:||December 20, 2022|
|Last Verified:||December 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Plan Description:||To Be determined|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Chimeric Antigen Receptor T-cell Therapy
Cytokine release syndrome
Immune effector Cell associated Neurotoxicity Syndrome
Acute lymphoblastic Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytokine Release Syndrome
Neoplasms by Histologic Type
Immune System Diseases
Neoplasms, Plasma Cell
Blood Protein Disorders
Nervous System Diseases
Systemic Inflammatory Response Syndrome