Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04975555
Recruitment Status : Recruiting
First Posted : July 23, 2021
Last Update Posted : November 30, 2021
Sponsor:
Information provided by (Responsible Party):
Mayur Narkhede, University of Alabama at Birmingham

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cytokine Release Syndrome ICANS Lymphoma, Non-Hodgkin Multiple Myeloma Acute Lymphoblastic Leukemia Drug: Siltuximab Phase 2

Detailed Description:
Patients eligible to receive CAR T-cell therapy for FDA-approved indications in hematological malignancies will be enrolled in this study on the day of CAR T-cell infusion. Patients will be followed until they develop grade 1 or higher CRS and/or ICANS. On developing these syndromes, siltuximab will be administered with close monitoring and follow-up for resolution of symptoms. If symptoms continue to worsen, then an additional dose of siltuximab will be given. If the symptoms leading to CRS do not resolve, then rescue tocilizumab will be administered. The study's primary endpoint is to assess the response rate of siltuximab in the resolution of CRS within 14 days. The study's secondary endpoint is to assess the response rate of siltuximab in the resolution of ICANS, the safety of siltuximab, and the overall response rate of CAR T-cell therapy.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: Siltuximab
Patients who experience CRS/ICANS will receive this treatment
Drug: Siltuximab
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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]



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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.

Exclusion Criteria:

  • 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.

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): NCT04975555


Contacts
Layout table for location contacts
Contact: Mayur Narkhede 205-934-2248 msnarkhede@uabmc.edu

Locations
Layout table for location information
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         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Layout table for investigator information
Principal Investigator: Mayur S Narkhede University of Alabama at Birmingham
Layout table for additonal information
Responsible Party: Mayur Narkhede, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04975555    
Other Study ID Numbers: IRB-300007103
First Posted: July 23, 2021    Key Record Dates
Last Update Posted: November 30, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: To Be determined

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mayur Narkhede, University of Alabama at Birmingham:
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:
Layout table for MeSH terms
Multiple Myeloma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Neurotoxicity Syndromes
Syndrome
Cytokine Release Syndrome
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Leukemia
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Systemic Inflammatory Response Syndrome
Inflammation