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

NCT04432506 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2019-1051NCI-2020-04369
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent High Grade B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory High Grade B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (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.

  Within 30 days after infusion of CAR T cells

Secondary Outcomes (5)

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

  30 days

• Overall Response Rate

  Up to 24 months

• Complete Response Rate

  Up to 24 months

• Progression Free Survival

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

• Overall Survival

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

Study Arms (1)

Treatment (cyclophosphamide, fludarabine, axi-cel, anakinra)

EXPERIMENTAL

Patients 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.

Biological: Anakinra; Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Anakinra BIOLOGICAL

Given SC

Also known as: Kinaret, Kineret, rIL-1ra, rIL1RN

Treatment (cyclophosphamide, fludarabine, axi-cel, anakinra)

Axicabtagene Ciloleucel BIOLOGICAL

Given IV

Also known as: KTE C19, KTE-C19, KTE-C19 CAR, Yescarta

Treatment (cyclophosphamide, fludarabine, axi-cel, anakinra)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (cyclophosphamide, fludarabine, axi-cel, anakinra)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (cyclophosphamide, fludarabine, axi-cel, anakinra)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma, Large B-Cell, Diffuse

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6; axicabtagene ciloleucel; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Paolo Strati, MD
• Organization: The University of Texas MD Anderson Cancer Center

pstrati@mdanderson.org

(713) 745-1776

Study Officials

• Paolo Strati

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 16, 2020
• Study Start: July 27, 2020
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2024-12

Locations

US (1)