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Anakinra for the Prevention of Cytokine Release Syndrome and Neurotoxicity in Patients With B-Cell Non-Hodgkin Lymphoma Receiving CD19-Targeted CAR-T Cell Therapy

Primary Purpose

B-Cell Non-Hodgkin Lymphoma

Status

Suspended

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Anakinra

About this trial

This is an interventional prevention trial for B-Cell Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must be 18 years of age or older
Karnofsky performance status of >= 60%
Patients with B-cell non-Hodgkin lymphoma (B-NHL) and eligible for treatment with liso-cel. Patients treated with non-conforming (out-of-specification) liso-cell may remain on study.
Negative serum pregnancy test within 2 weeks of enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
Fertile male and female subjects must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of anakinra
Ability to understand and provide informed consent

Exclusion Criteria:

Subjects requiring ongoing daily corticosteroid therapy at a dose of > 15 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)
Known hypersensitivity to Escherichia € coli-derived proteins, anakinra, or to any component of the product
Major organ dysfunction defined as:
- Serum creatinine > 2.5 mg/dL
- Significant hepatic dysfunction (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 5x upper limit of normal; bilirubin > 3.0 mg/dL) unless due to malignancy or Gilbert's syndrome in the opinion of the PI or designee
- Subjects with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with a forced expiratory volume in 1 second (FEV1) of < 50% of predicted or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% will be excluded
- Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < 35%
Uncontrolled serious and active infection

Sites / Locations

Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prevention (anakinra, lisocabtagene maraleucel)

Arm Description

Patients receive anakinra SC daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0.

Outcomes

Primary Outcome Measures

Absence of any grade cytokine release syndrome (CRS)

Will assess the efficacy of anakinra in preventing the occurrence of any grade CRS using the Bayesian optimal phase 2 design. Assessed based on the ASTCT Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

Secondary Outcome Measures

CRS grade

Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

Neurotoxicity grade

Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

Rate of hospitalization after liso-cel treatment

Duration of hospitalization after liso-cel treatment

Corticosteroid usage after liso-cel treatment

Disease response to liso-cel

Objective responses to the therapeutic regimen will be assessed based on institutional standard using physical examination, imaging (CT or PET-CT), and if necessary, bone marrow biopsies.

Adverse events (AEs)

Grade 3 or greater AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Full Information

NCT ID

NCT04359784

First Posted

April 15, 2020

Last Updated

April 4, 2023

Sponsor

Fred Hutchinson Cancer Center

Collaborators

Swedish Orphan Biovitrum

1. Study Identification

Unique Protocol Identification Number

NCT04359784

Brief Title

Anakinra for the Prevention of Cytokine Release Syndrome and Neurotoxicity in Patients With B-Cell Non-Hodgkin Lymphoma Receiving CD19-Targeted CAR-T Cell Therapy

Official Title

Phase 2 Pilot Study to Evaluate Efficacy and Safety of Anakinra to Prevent CD19-Targeted CAR-T Cell-Related Cytokine Release Syndrome (CRS) and Neurotoxicity in Patients With B Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Suspended

Why Stopped

Recruitment on hold while awaiting negotiation to increase accrual.

Study Start Date

December 27, 2021 (Actual)

Primary Completion Date

March 3, 2024 (Anticipated)

Study Completion Date

March 3, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fred Hutchinson Cancer Center

Collaborators

Swedish Orphan Biovitrum

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II trial studies how well anakinra works in decreasing the occurrence of cytokine release syndrome (CRS) and damage to the nerves (neurotoxicity) in patients with B-cell non-Hodgkin lymphoma who are receiving CD-19 targeted chimeric antigen receptor T-cell (CAR-T) therapy. CAR-T cell therapy may be complicated by two potentially life-threatening side effects: CRS and neurotoxicity. Anakinra is a drug typically used to treat rheumatoid arthritis, but may also help in preventing CAR-T cell-related cytokine release syndrome and neurotoxicity.

Detailed Description

OUTLINE: Patients receive anakinra subcutaneously (SC) daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. After completion of lisocabtagene maraleucel infusion, patients are followed up periodically for up to 90 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B-Cell Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Prevention (anakinra, lisocabtagene maraleucel)

Arm Type

Experimental

Arm Description

Patients receive anakinra SC daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0.

Intervention Type

Biological

Intervention Name(s)

Anakinra

Other Intervention Name(s)

Kinaret, Kineret, rIL-1ra, rIL1RN, 143090-92-0

Intervention Description

Given SC

Primary Outcome Measure Information:

Title

Absence of any grade cytokine release syndrome (CRS)

Description

Time Frame

Up to 28 days after lisocabtagene maraleucel (liso-cel) infusion

Secondary Outcome Measure Information:

Title

CRS grade

Description

Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

Time Frame

Up to 28 days after liso-cel infusion

Title

Neurotoxicity grade

Description

Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

Time Frame

Up to 28 days after liso-cel infusion

Title

Rate of hospitalization after liso-cel treatment

Time Frame

Up to 28 days after liso-cel infusion

Title

Duration of hospitalization after liso-cel treatment

Time Frame

Up to 28 days after liso-cel infusion

Title

Corticosteroid usage after liso-cel treatment

Time Frame

Up to 28 days after liso-cel infusion

Title

Disease response to liso-cel

Description

Objective responses to the therapeutic regimen will be assessed based on institutional standard using physical examination, imaging (CT or PET-CT), and if necessary, bone marrow biopsies.

Time Frame

Approximately at 28 and 90 days after liso-cel infusion

Title

Adverse events (AEs)

Description

Grade 3 or greater AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Time Frame

Up to 28 days after liso-cel infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must be 18 years of age or older Karnofsky performance status of >= 60% Patients with B-cell non-Hodgkin lymphoma (B-NHL) and eligible for treatment with liso-cel. Patients treated with non-conforming (out-of-specification) liso-cell may remain on study. Negative serum pregnancy test within 2 weeks of enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year Fertile male and female subjects must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of anakinra Ability to understand and provide informed consent Exclusion Criteria: Subjects requiring ongoing daily corticosteroid therapy at a dose of > 15 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) Known hypersensitivity to Escherichia € coli-derived proteins, anakinra, or to any component of the product Major organ dysfunction defined as: Serum creatinine > 2.5 mg/dL Significant hepatic dysfunction (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 5x upper limit of normal; bilirubin > 3.0 mg/dL) unless due to malignancy or Gilbert's syndrome in the opinion of the PI or designee Subjects with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with a forced expiratory volume in 1 second (FEV1) of < 50% of predicted or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% will be excluded Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < 35% Uncontrolled serious and active infection

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jordan Gauthier

Organizational Affiliation

Fred Hutch/University of Washington Cancer Consortium

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fred Hutch/University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Anakinra for the Prevention of Cytokine Release Syndrome and Neurotoxicity in Patients With B-Cell Non-Hodgkin Lymphoma Receiving CD19-Targeted CAR-T Cell Therapy

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