A Phase II, Open-Label, Single Arm Trial to Assess The Efficacy and Safety of the Combination of Tisagenlecleucel And Ibrutinib in Mantle Cell Lymphoma

Peter MacCallum Cancer Centre, Australia1 site in 1 country20 target enrollmentApril 7, 2020

ConditionsMantle Cell Lymphoma Recurrent

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Mantle Cell Lymphoma Recurrent
Sponsor: Peter MacCallum Cancer Centre, Australia
Enrollment: 20
Locations: 1
Primary Endpoint: Estimate complete response (CR) rate at month 4 following the infusion of Tisagenlecleucel using the Lugano criteria
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open label, multi-center, single-arm, phase II study investigating the efficacy and safety of the combination of ibrutinib and Tisagenlecleucel in twenty patients with relapsed or refractory Mantle Cell Lymphoma (MCL) or who had sub-optimal response to standard therapy in the presence of TP53 mutation.

Registry

clinicaltrials.gov

Start Date

April 7, 2020

End Date

September 1, 2030

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Peter MacCallum Cancer Centre, Australia

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must meet all the following criteria for study entry:
•Written informed consent prior to screening procedures
•Be ≥18 years of age on the day of signing informed consent
•Have a confirmed diagnosis of MCL according to World Health Organization (2016) criteria
•Have sufficient fresh or archival material available for central review
•At least one site of radiographically assessable disease not previously irradiated (lymph node with largest diameter ≥1.5cm, or unequivocal evaluable hepatomegaly/splenomegaly or marrow phase disease)
•Meet at least one of the following disease criteria:
•Have relapsed, or progressed following at least 1 prior line of systemic chemoimmunotherapy for MCL (may include ibrutinib or other BTK-inhibitor in combination)
•Be refractory to at least one prior line of chemoimmunotherapy (refractory is defined as less than a conventional PR following 2 cycles of anthracycline or cytarabine-containing therapy)
•Have achieved \<CR on PET imaging following 2 cycles of anthracycline or cytarabine-containing therapy in the presence of aberrations of p53; or \<CR post autologous stem cell transplantation

Exclusion Criteria

•Patients who meet any of the following criteria will be excluded from study entry:
•Prior allogeneic transplantation
•Autologous transplantation within 6 weeks prior to registration
•Active and uncontrolled autoimmune cytopenias
•Active central nervous system involvement with MCL
•Previous treatment with adoptive T-cell therapy
•Receipt of a non BTK-inhibitor investigational medical product within the last 30 days prior to planned leukapheresis
•Receipt of a non-anti CD20- monoclonal antibody with anti-neoplastic intent within 30 days prior to planned leukapheresis
•Receipt of steroids \>20mg prednisolone or equivalent in the fortnight prior to planned leukapheresis
•Requirement for ongoing therapy with:

Outcomes

Primary Outcomes

Estimate complete response (CR) rate at month 4 following the infusion of Tisagenlecleucel using the Lugano criteria

Time Frame: 4 months after Tisagenlecleucel infusion using the Lugano criteria

Using the Lugano criteria

Secondary Outcomes

Evaluate safety of combination therapy with Tisagenlecleucel and ibrutinib through monitoring of the incidence, nature and severity of adverse events (graded according to NCI CTCAE v5.0), SAEs, dose interruptions and dose reductions of ibrutinib(From date of registration until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date of the patient's last annual assessment, on average for five years)
To estimate overall survival(From date of registration until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date of the patient's last annual assessment, on average for five years)
Estimate objective response (OR) rate at day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel using Lugano criteria(day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel)
To estimate objective response (OR) rate at day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel by TP53 status(day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel by TP53 status)
To estimate Minimal Residual Disease (MRD) negative response rates by aggregate measure of peripheral blood/or bone marrow flow cytometry, PCR and ctDNA(At day 28, months 4, 6, 9 and 12 following the infusion of Tisagenlecleucel)
To estimate progression-free survival(From date of registration until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date of the patient's last annual assessment, on average for five years)
To estimate duration of response(From date of registration until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date of the patient's last annual assessment, on average for five years)