AzTrials
AzTrials

Hematopoietic and Lymphoid Cell NeoplasmPhase 2NCT04432506

Anakinra for the Reduction of CAR-T Toxicity in Patients With Relapsed or Refractory Large B-cell Lymphoma

A Phase 2 study testing Anakinra, Axicabtagene Ciloleucel and Cyclophosphamide in people with Hematopoietic and Lymphoid Cell Neoplasm and Recurrent Diffuse Large B-Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies the side effects and best dose of anakinra and to see how well it works in reducing side effects (toxicity) associated with a CAR-T cell treatment called axicabtagene ciloleucel in patients with large B-cell lymphoma that has come back (relapsed) or has not responded to treatment… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anakinra, Axicabtagene Ciloleucel and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
27 Jul 2020to 28 May 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), or high-grade B-cell lymphoma (HGBCL), at least 2 prior lines of systemic therapy
  • Planned to receive standard of care therapy with axicabtagene ciloleucel
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Measurable disease of >= 1.5 cm
  • At least two weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for axicabtagene ciloleucel (axi-cel) therapy, except for systemic immune checkpoint inhibitory / immune stimulatory therapy. At least 3 half-lives must have elapsed from any prior systemic immune checkpoint inhibitory / immune stimulatory 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)
Show all 15Show fewer
  • Absolute neutrophil count of >= 1.0 x 10^9/L
  • Platelet count of >= 60 x 10^9/L
  • Creatinine clearance (as estimated by Cockcroft Gault) >= 45 mL/minute (min)
  • Serum alanine transaminase (ALT) / aspartate transaminase (AST) =< 2.5 upper limit of normal (ULN)
  • Total bilirubin =< 1.5 mg/dL, except in subjects with Gilbert's syndrome
  • Cardiac ejection fraction >= 50% with no evidence of pericardial effusion
  • Baseline oxygen saturation > 92% on room air
  • No evidence, suspicion, and/or history of lymphoma involving the central nervous system (CNS)
  • 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)

Who cannot join

  • History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
  • History of Richter's transformation of chronic lymphocytic leukemia (CLL)
  • Autologous stem cell transplantation within 6 weeks of planned axi-cel infusion
  • History of allogeneic stem cell transplantation
  • Prior CD19 targeted therapy
  • Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
Show all 24Show fewer
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the principal investigator
  • Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B virus surface antigen [HBsAg] positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing
  • Known history of tuberculosis. A negative Quantiferon or purified protein derivative (PPD) up to 2 months before start of anakinra is enough if no specific risk factors
  • 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, 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
  • Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression
  • Primary immunodeficiency
  • 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
  • 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, including E coli-derived proteins
  • 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
  • Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of anakinra injections
  • In the investigator's 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 Trial Treatments

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Pilot Study of Anakinra to Mitigate CAR-T Toxicity in Subjects With Relapsed or Refractory Large B-Cell Lymphoma

This phase II trial studies the side effects and best dose of anakinra and to see how well it works in reducing side effects (toxicity) associated with a CAR-T cell treatment called axicabtagene ciloleucel in patients with large B-cell lymphoma that has come back (relapsed) or has not responded to treatment (refractory). Anakinra is a drug typically used to treat rheumatoid arthritis but may also help in reducing CAR-T cell therapy toxicity. Giving anakinra in combination with axicabtagene ciloleucel may help control relapsed or refractory large B-cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess safety and tolerability of anakinra in reducing incidence of cytokine release syndrome (CRS) within 30 days after infusion of chimeric antigen receptor (CAR) T cells in subjects with relapsed or refractory large B-cell lymphoma.

SECONDARY OBJECTIVES:

  1. To determine incidence of all grades and duration of both CRS and immune-cell associated neurotoxicity syndrome (ICANS).

II. To determine the complete response rate (CRR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. To determine the effects of anakinra on the cytokine and chemokine profile in peripheral blood after CAR-T therapy.

II. To determine the effects of anakinra on the expansion and persistence of CAR T cells.

III. To correlate baseline characteristics with toxicity, response and survival after anakinra combined with CAR-T therapy.

OUTLINE: This is a dose-escalation study of anakinra.

Patients receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive axicabtagene ciloleucel IV over 30 minutes or less on day 0 and anakinra subcutaneously (SC) on days 0-6 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 and 4 weeks, and then at 2, 3, 6, 9, 12, 18, and 24 months.

Being tested
Anakinra, Axicabtagene Ciloleucel, Cyclophosphamide, Fludarabine
Medical subject headings
Hematologic Neoplasms, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraBiological

    Also called Kinaret, Kineret, rIL-1ra, rIL1RN

    Given SC

  • Axicabtagene CiloleucelBiological

    Also called KTE C19, KTE-C19, KTE-C19 CAR, Yescarta

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

Study groups in NCT04432506
Study groupRoleWhat they receive
Treatment (cyclophosphamide, fludarabine, axi-cel, anakinra)ExperimentalPatients receive cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive axicabtagene ciloleucel IV over 30 minutes or less on day 0 and anakinra SC on days 0-6 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Anakinra; Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Any Grade Cytokine Release Syndrome (CRS)

    Will be tabulated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version (v)5.0. CRS will be assessed by both Lee 2014 criteria as well as American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading system.

    Measured: Within 30 days after infusion of CAR T cells

Secondary outcomes (5)

  1. Incidence of Different Grades and Duration of Both CRS and Immune Cell-associated Neurotoxicity Syndrome (ICANS)

    Will be tabulated according to the NCI CTCAE v5.0. CRS will be assessed by both Lee 2014 criteria as well as ASTCT Consensus Grading system. ICANS will be assessed by both CTCAE v5.0 as well as ASTCT Consensus Grading system.

    Measured: 30 days

  2. Overall Response Rate

    Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma.

    Measured: Up to 24 months

  3. Complete Response Rate

    Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma.

    Measured: Up to 24 months

  4. Progression Free Survival

    Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma. Will be estimated using the method of Kaplan and Meier.

    Measured: From the start of treatment to disease progression or death due to any cause whichever happened first, assessed up to 24 months

  5. Overall Survival

    Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma. Will be estimated using the method of Kaplan and Meier.

    Measured: From the start of treatment to death due to any cause, assessed up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2020
  2. Study start27 Jul 2020
  3. Primary completion28 May 2024
  4. Study completion28 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04432506
Sponsor's protocol ID
2019-1051
Other IDs
NCI-2020-04369, 2019-1051
Status last verified
Dec 2024
First submitted
11 Jun 2020
Last updated
28 Jan 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra, Axicabtagene Ciloleucel and Cyclophosphamide in people with Hematopoietic and Lymphoid Cell Neoplasm and Recurrent Diffuse Large B-Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Any Grade Cytokine Release Syndrome (CRS) (time frame: Within 30 days after infusion of CAR T cells). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04432506.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in