- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04150913
A Phase 2 Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxicity
This research study is studying the combination of anakinra and axicabtagene ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities with relapsed or refractory Non-Hodgkin lymphoma (NHL).
- Relapsed NHL is the condition of returned Non-Hodgkin lymphoma.
- Refractory NHL is the condition of previous treatment resistant Non-Hodgkin lymphoma.
- Cytokine Release Syndrome (CRS) is a group of side effect symptoms that can include nausea, headache, rapid heartbeat, shortness of breath, kidney damage, and rash.
- Neurologic toxicity is nervous system disorder characterized by confusion
This research study involves two drugs:
- Anakinra
- Axicabtagene Ciloleucel.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This Phase 2, single center, open-label research study is studying the combination of Anakinra and Axicabtagene Ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities in people with relapsed or refractory Non-Hodgkin lymphoma (NHL).
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
This research study involves two drugs:
- Anakinra
- Axicabtagene Ciloleucel
- A total of 20 participants will be enrolled to this trial
- The U.S. Food and Drug Administration (FDA) has not approved anakinra for use in treatment of Non-Hodgkin lymphoma (NHL).
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
-
Boston, Massachusetts, United States, 02115
- Massachusetts General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
- At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma 1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy however steroids only require a 7-day washout. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc).
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)
- Age 18 or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- ANC ≥1000/uL
- Platelet count ≥75,000/uL
- Absolute lymphocyte count ≥100/uL
Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
- Serum ALT/AST ≤2.5 ULN
- Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome.
- Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion, and no clinically significant ECG findings
- No clinically significant pleural effusion
- Baseline oxygen saturation >92% on room air
- Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
- History of Richter's transformation of CLL
- Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion
- History of allogeneic stem cell transplantation
- Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for re-treatment
- Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
- History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
- Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
- History of HIV infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines.
- Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
- Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
- History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
- Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)
- Primary immunodeficiency
- History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
- Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
- History of severe immediate hypersensitivity reaction to any of the agents used in this study
- Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
- Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of axicabtagene ciloleucel
- In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
- History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Anakinra and Axicabtagene Ciloleucel
Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment.
|
Subcutaneous, dosage per protocol.
Day 0 through Day 6.
Other Names:
Once, intravenous infusion, dosage per protocol
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of neurotoxicity as per CTCAE v4.03 criteria
Time Frame: 30 Days
|
The incidence of grade 2+ neurotoxicity will be assessed in comparison to a historical rate of 45% via a two-sized exact binomial test with significant level of 0.05.
|
30 Days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate
Time Frame: 24 Months
|
The incidence of objective response and exact 2-sided 95% confidence intervals will be generated
|
24 Months
|
Duration of Response
Time Frame: first objective response to disease progression death regardless of cause up 100 Months
|
Cumulative incidence of relapse.
|
first objective response to disease progression death regardless of cause up 100 Months
|
Progression-free Survival
Time Frame: infusion date to the date of disease progression or death from any cause up 100 Months
|
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for progression-free survival time
|
infusion date to the date of disease progression or death from any cause up 100 Months
|
Overall Survival
Time Frame: time from axicabtagene ciloleucel infusion to the date of death or analysis data cutoff date will be censored at last contact date up to 100 months.
|
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS.
|
time from axicabtagene ciloleucel infusion to the date of death or analysis data cutoff date will be censored at last contact date up to 100 months.
|
Number of Participants with Adverse Events CTCAE version 4.03 Grade 3 or higher
Time Frame: 24 Months
|
Subject incidence rates of adverse events including all, serious, fatal, CTCAE version 4.03 Grade 3 or higher and treatment related AEs reported throughout the conduct of the study will be tabulated by preferred term and system organ class
|
24 Months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Matt J Frigault, MD, Massachusetts General Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Systemic Inflammatory Response Syndrome
- Inflammation
- Disease
- Shock
- Poisoning
- Lymphoma
- Syndrome
- Lymphoma, Non-Hodgkin
- Neurotoxicity Syndromes
- Cytokine Release Syndrome
- Antirheumatic Agents
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Interleukin 1 Receptor Antagonist Protein
- Axicabtagene ciloleucel
Other Study ID Numbers
- 19-348
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Non Hodgkin Lymphoma
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin LymphomaUnited States
-
Marker Therapeutics, Inc.RecruitingNon Hodgkin Lymphoma | Non-Hodgkin Lymphoma, Adult | Non-Hodgkin Lymphoma, Refractory | Non-Hodgkin Lymphoma, RelapsedUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell LymphomaUnited States
-
National Cancer Institute (NCI)RecruitingRefractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Primary Cutaneous... and other conditionsUnited States
-
Caribou Biosciences, Inc.RecruitingLymphoma | Lymphoma, Non-Hodgkin | B Cell Lymphoma | Non Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Relapsed Non Hodgkin Lymphoma | B Cell Non-Hodgkin's LymphomaUnited States, Australia, Israel
-
Mayo ClinicNot yet recruitingIndolent B-Cell Non-Hodgkin Lymphoma | Recurrent Indolent Non-Hodgkin Lymphoma | Refractory Indolent Non-Hodgkin Lymphoma | Recurrent Indolent B-Cell Non-Hodgkin Lymphoma | Refractory Indolent B-Cell Non-Hodgkin LymphomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingRefractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Hematopoietic Cell Transplantation RecipientUnited States
-
University of WashingtonRecruitingRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin LymphomaUnited States
-
Chongqing Precision Biotech Co., LtdRecruitingNon Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Relapsed Non-Hodgkin LymphomaChina
-
Estrella Biopharma, Inc.Eureka Therapeutics Inc.Not yet recruitingLymphoma | Lymphoma, Non-Hodgkin | Non-Hodgkin's Lymphoma | Non-Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | High-grade B-cell Lymphoma | CNS Lymphoma | Lymphomas Non-Hodgkin's B-Cell | Relapsed Non-Hodgkin Lymphoma | Lymphoma, Non-Hodgkins | Large B-Cell Lymphoma and other conditions
Clinical Trials on Anakinra
-
Virginia Commonwealth UniversityAmerican Heart AssociationCompleted
-
University of AthensCompletedCoronary Artery Disease | Inflammation | Rheumatoid ArthritisGreece
-
Weill Medical College of Cornell UniversitySwedish Orphan BiovitrumWithdrawnCovid19 | Mechanical Ventilation Complication | Cytokine StormUnited States
-
University of North Carolina, Chapel HillNational Heart, Lung, and Blood Institute (NHLBI)Withdrawn
-
Virginia Commonwealth UniversityNational Heart, Lung, and Blood Institute (NHLBI)CompletedHeart FailureUnited States
-
University of North Carolina, Chapel HillNational Heart, Lung, and Blood Institute (NHLBI)Withdrawn
-
National Institute of Neurological Disorders and...CompletedMultiple SclerosisUnited States
-
National Institute of Arthritis and Musculoskeletal...CompletedImmune System Diseases | Autoimmune Connective Tissue DisorderUnited States
-
National Institute of Allergy and Infectious Diseases...TerminatedEczema | Atopic Dermatitis | Allergic Disease | Anakinra | KineretUnited States