Ignite Creation Date:
2024-05-06 @ 6:57 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05840289
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-05-06
First Post:
2023-04-21
Brief Title:
A Study on Fractionated Rituximab to Avoid Lysis Syndrome in Aggressive B-Lymphoma
Sponsor:
University Hospital Geneva
Organization:
University Hospital Geneva
Study Overview
Official Title:
FRILLY A Retrospective Single-centre Study on Fractionated Rituximab to Avoid Lysis Syndrome in Aggressive B-Lymphoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FRILLY
Brief Summary:
Tumour lysis syndrome TLS occurs as a consequence of the rapid destruction of malignant cells spontaneously andor in response to cytotoxic agents and immunotherapies TLS is a feature of highly proliferative diseases with heavy tumor burden such as high-grade non-Hodgkin lymphomas NHL typically Burkitts lymphoma We evaluated fractionating first rituximab dose to prevent TLS in a real-life B-cell NHL cohort of patients treated at University Hospital of Geneva between 2010 and 2020
Detailed Description:
Tumour lysis syndrome TLS occurs as a consequence of the rapid destruction of malignant cells spontaneously andor in response to cytotoxic agents and immunotherapies TLS is a feature of highly proliferative diseases with heavy tumor burden such as acute lymphoblastic leukemia B-ALL and high-grade non-Hodgkin lymphomas NHL typically Burkitts lymphoma TLS usually develop during the first week of treatment due to the sudden release of intracellular ions nucleic acids and protein metabolites These metabolic disturbances can manifest as hyperuricemia hyperkaliemia hyperphosphatemia hypocalcemia and uremia exposing the patient to acute renal insufficiency lactic acidosis and ultimately death in the absence of appropriate management
In order to make them more practical and reproducible TLS criteria were modified in 2004 by Cairo and Bishop who also developed a grading classification as 1 biochemical TLS occurring 3 days before to 7 days after the start of therapy and 2 clinical TLS in case of seizure cardiac arrhythmia or significant acute renal injury AKI TLS is burdened with significant morbidity and mortality
Historically TLS incidence among high-grade non-Hodgkins lymphoma NHL patients was reported in as high as 42 of cases with 6 of clinically significant TLS In a more recent multicentric retrospective analysis performed on 722 patients 37 NHL 36 ALL 27 AML 52 of the patients developed TLS and among them 25 required intensive care unit admission with a relative mortality rate of 15
Rituximab Mabthera Swissmedic 54378 is a therapeutic monoclonal antibody that binds with high affinity to cells expressing the CD20 antigen found on the surface of malignant and normal B cells inducing complement-dependent and antibody-dependent cellular cytotoxicity Approved in 1997 for the treatment of CD20-positive B-cell low-grade NHL rituximab is now widely used in all the spectrum of B-cell malignancies Initially administered on a weekly schedule for a total of 4 to 8 infusions rituximab is currently infused together with other cytotoxic agents every 3 to 4 weeks Rituximab may cause a massive cytolysis of B-cells in some patients leading to an acute onset TLS Notably TLS was reported as the second significant safety signal after rituximab administration in 1998
Since the development of uricolytic agents rasburicase TLS incidence has significantly been reduced Nevertheless early risk-stratification and initiation of a comprehensive supportive care are mandatory in TLS The mainstays of TLS prophylaxis and treatment include hydration and diuresis control of hyperuricaemia with xanthine oxidase inhibitors blocking endogenous uric acid production from purine nucleotides eg allopurinol or uricolytic agents rasburicase and vigilant monitoring of electrolyte abnormalities
In addition preemptive strategies of tumor debulking were developed such as steroids or low-dose chemotherapy prophase or gradual dose ramp-up of the cytotoxic agent as exemplified with the administration of the Bcl2 inhibitor Venetoclax in chronic lymphocytic leukemia
To prevent TLS but also other side effects such as allergy and cytokine-release syndrome during the first administration of rituximab a few studies suggested the use of a fractionated and dose ramp-up schedule of rituximab administration in B-cell malignancies In Geneva University Hospital HUG this strategy was widely applied to most cases of patients having a B-cell malignancy at high-risk for TLS since the publication of these pioneer studies We aim at investigating the incidence and severity of TLS in high-grade B-cell lymphoma patients treated at HUG over the last ten years
Main objective To evaluate the incidence of biochemical lysis syndrome LTLS and clinical lysis syndrome CTLS in patients receiving fractionated Rituximab infusion for high-grade B-cell lymphoma
Inclusion
Newly diagnosed or relapsing histologically proven B-cell lymphoma patients treated with fractionated Rituximab infusion considered as 2 consecutive infusions at least 24 hours apart
Exclusion
Unproven histologically B-cell lymphoma
Patients who receive a single day Rituximab infusion
Patients under long-term dialysis before Rituximab started
Age 18 years
Absence of written informed consent
In order to make them more practical and reproducible TLS criteria were modified in 2004 by Cairo and Bishop who also developed a grading classification as 1 biochemical TLS occurring 3 days before to 7 days after the start of therapy and 2 clinical TLS in case of seizure cardiac arrhythmia or significant acute renal injury AKI TLS is burdened with significant morbidity and mortality
Historically TLS incidence among high-grade non-Hodgkins lymphoma NHL patients was reported in as high as 42 of cases with 6 of clinically significant TLS In a more recent multicentric retrospective analysis performed on 722 patients 37 NHL 36 ALL 27 AML 52 of the patients developed TLS and among them 25 required intensive care unit admission with a relative mortality rate of 15
Rituximab Mabthera Swissmedic 54378 is a therapeutic monoclonal antibody that binds with high affinity to cells expressing the CD20 antigen found on the surface of malignant and normal B cells inducing complement-dependent and antibody-dependent cellular cytotoxicity Approved in 1997 for the treatment of CD20-positive B-cell low-grade NHL rituximab is now widely used in all the spectrum of B-cell malignancies Initially administered on a weekly schedule for a total of 4 to 8 infusions rituximab is currently infused together with other cytotoxic agents every 3 to 4 weeks Rituximab may cause a massive cytolysis of B-cells in some patients leading to an acute onset TLS Notably TLS was reported as the second significant safety signal after rituximab administration in 1998
Since the development of uricolytic agents rasburicase TLS incidence has significantly been reduced Nevertheless early risk-stratification and initiation of a comprehensive supportive care are mandatory in TLS The mainstays of TLS prophylaxis and treatment include hydration and diuresis control of hyperuricaemia with xanthine oxidase inhibitors blocking endogenous uric acid production from purine nucleotides eg allopurinol or uricolytic agents rasburicase and vigilant monitoring of electrolyte abnormalities
In addition preemptive strategies of tumor debulking were developed such as steroids or low-dose chemotherapy prophase or gradual dose ramp-up of the cytotoxic agent as exemplified with the administration of the Bcl2 inhibitor Venetoclax in chronic lymphocytic leukemia
To prevent TLS but also other side effects such as allergy and cytokine-release syndrome during the first administration of rituximab a few studies suggested the use of a fractionated and dose ramp-up schedule of rituximab administration in B-cell malignancies In Geneva University Hospital HUG this strategy was widely applied to most cases of patients having a B-cell malignancy at high-risk for TLS since the publication of these pioneer studies We aim at investigating the incidence and severity of TLS in high-grade B-cell lymphoma patients treated at HUG over the last ten years
Main objective To evaluate the incidence of biochemical lysis syndrome LTLS and clinical lysis syndrome CTLS in patients receiving fractionated Rituximab infusion for high-grade B-cell lymphoma
Inclusion
Newly diagnosed or relapsing histologically proven B-cell lymphoma patients treated with fractionated Rituximab infusion considered as 2 consecutive infusions at least 24 hours apart
Exclusion
Unproven histologically B-cell lymphoma
Patients who receive a single day Rituximab infusion
Patients under long-term dialysis before Rituximab started
Age 18 years
Absence of written informed consent
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None