Clinical Trial to Assess The Efficacy and Safety of the Combination of Tisagenlecleucel And Ibrutinib in Mantle Cell Lymphoma

NCT04234061 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 19/008
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Mantle Cell Lymphoma Recurrent

Keywords

ibrutinib; Tisagenlecleucel; Chimeric Antigen Receptor - Tcell (CAR-T); B-cell non-Hodgkin lymphoma; TP53 mutation; bruton's tyrosine kinase (BTK) inhibitor

Outcome Measures

Primary Outcomes (1)

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

  Using the Lugano criteria

  4 months after Tisagenlecleucel infusion using the Lugano criteria

Secondary Outcomes (7)

• 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

• 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

Study Arms (1)

Single

EXPERIMENTAL

ibrutinib and Tisagenlecleucel

Combination Product: ibrutinib and Tisagenlecleucel

Interventions

ibrutinib and Tisagenlecleucel COMBINATION_PRODUCT

Single-arm study investigating combination of ibrutinib and Tisagenlecleucel treatment

Single

Eligibility Criteria

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

You may qualify if:

• 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
• Failure to achieve CR following at least 6 months of an ibrutinib or BTK inhibitor -containing front-line regimen, or failure to achieve PR following 8 weeks of a BTK inhibitor
• Have a life expectancy of ≥ 3 months, as judged by the investigator
• Have acceptable haematological function within 7 days prior to registration, defined as:
• Absolute neutrophil count ≥1x10\^9/L (may be supported by growth)
• Absolute lymphocyte count ≥0.3x10\^9/L or absolute CD3+ fraction \> 0.15x 10\^9/L

You may not qualify if:

• 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:
• Potent CYP3A inhibitors (e.g. indinavir, ketoconazole, clarithromycin)
• Potent CYP3A inducers (e.g. rifampin, phenytoin, carbamazepine)
• Vitamin K antagonists (e.g. warfarin or equivalent)
• Antiretroviral medications
• Consumption within 3 days prior to registration:

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Novartis: collaborator

Study Sites (1)

Peter Mac Callum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

Related Publications (1)

• Minson A, Hamad N, Cheah CY, Tam C, Blombery P, Westerman D, Ritchie D, Morgan H, Holzwart N, Lade S, Anderson MA, Khot A, Seymour JF, Robertson M, Caldwell I, Ryland G, Saghebi J, Sabahi Z, Xie J, Koldej R, Dickinson M. CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: the phase 2 TARMAC study. Blood. 2024 Feb 22;143(8):673-684. doi: 10.1182/blood.2023021306.

  PMID: 37883795 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

ibrutinib; tisagenlecleucel

Condition Hierarchy (Ancestors)

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

Study Officials

• Michael Dickinson

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: single arm

Study Record Dates

• First Submitted: January 5, 2020
• First Posted: January 21, 2020
• Study Start: April 7, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2030
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)