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Mantle Cell Lymphoma RecurrentPhase 2TARMACNCT04234061

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

A Phase 2 study testing ibrutinib and Tisagenlecleucel in people with Mantle Cell Lymphoma Recurrent, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle Cell Lymphoma Recurrent
What is being tested?
ibrutinib and Tisagenlecleucel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteAustralia
Study dates
7 Apr 2020to 1 Sep 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • 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)
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  • 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
  • Platelets >50x 10^9/L unless explained by lymphoma at the discretion of the CPI
  • Haemoglobin ≥ 80 g/L (may be transfusion supported)
  • Have acceptable organ function within 7 days prior to registration, defined as:
  • Serum creatinine ≤1.5 x ULN, or a calculated creatinine clearance of at least 50 mL/min using the Cockcroft-Gault equation (see appendix 1) or a 24-hour urine collection
  • AST or ALT ≤3.0 x ULN
  • Bilirubin ≤ 1.5 x ULN (with the exception of patients with Gilbert's syndrome. Patients with Gilbert's syndrome may be included if their total bilirubin is ≤3.0 x ULN and direct bilirubin ≤1.5 x ULN).
  • aPTT and PT ≤ 1.5x ULN
  • Adequate pulmonary function defined as:
  • No or mild dyspnea (≤ grade 1)
  • Oxygen saturation measured by pulse oximetry ≥ 90 percent on room air 10. Female patients of childbearing potential and non-sterile male patients (with partners of childbearing potential) must agree to use highly effective methods of contraception from registration on the study to 30 days after the last dose of ibrutinib and 12 months after Tisagenlecleucel infusion and until Tisagenlecleucel is no longer present by qPCR on two consecutive tests (whichever is later):
  • Total abstinence from sexual intercourse when this is in line with the preferred and usual life style of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to registration. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment
  • Male sterilisation (at least 6 months prior to screening). For female patients on the study, the vasectomised male partner should be the sole partner for that patient
  • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before enrolment into this study.
  • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child bearing potential.
  • 11. Female patients of childbearing potential must have a negative serum (beta-human chorionic gonadotropin (β-hCG) or urine pregnancy test within 7 days of registration 12. Sexually active male patients must use a condom during intercourse and must agree to refrain from sperm donation, from registration on the study until 30 days after the last dose of ibrutinib or 12 months after Tisagenlecleucel infusion and until Tisagenlecleucel is no longer present by qPCR on two consecutive tests

Who cannot join

  • 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
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  • 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:
  • Grapefruit or grapefruit products
  • Seville oranges
  • Star fruit
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months of screening or class III to IV cardiac disease as defined by the New York Heart Association Functional Classification
  • Active neurological disorders of clinical relevance (e.g. epilepsy, severe brain injury, dementia, Parkinson's disease or autoimmune/inflammatory disorders (e.g. Guillain-Barre syndrome, motor neurone disease, chronic inflammatory demyelinating polyneuropathy)
  • Other significant life-threatening illness or medical condition which, in the investigator's opinion, could compromise the subject's safety, interfere with absorption or metabolism of study drug, or put the study outcomes at undue risk
  • History of other active malignancy, with the exception of:
  • Adequately treated in situ carcinoma of the cervix or breast
  • Adequately treated basal cell carcinoma of skin or localised squamous cell carcinoma of the skin
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and without evidence of recurrence for at least 2 years prior to registration
  • History of human immunodeficiency (HIV) or active hepatitis C virus or active hepatitis B virus. NOTE: Serology must be repeated at the pre-conditioning stage prior to infusion with Tisagenlecleucel.
  • Clinically significant active infection confirmed by clinical evidence, imaging or positive laboratory tests (e.g. blood cultures, viral DNA/RNA by PCR)
  • Receipt of live, attenuated vaccines within 4 weeks of registration
  • Major surgery within 4 weeks prior to registration
  • Pregnant or nursing (lactating) women. Note: Women of child-bearing potential must have a negative serum pregnancy test performed within 24 hours before leukapheresis, lymphodepletion (if performed) and prior to Tisagenlecleucel infusion.
  • Known hypersensitivity to the excipients of Tisagenlecleucel or to any product to be given to the patient as per the study protocol (e.g. tocilizumab and lymphodepleting agents)

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Peter Mac Callum Cancer Centre

    Melbourne, Victoria, 3002

Other trials in Australia

About this study

Official title: 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

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.

Being tested
ibrutinib and Tisagenlecleucel
Keywords
ibrutinib, Tisagenlecleucel, Chimeric Antigen Receptor - Tcell (CAR-T), B-cell non-Hodgkin lymphoma, TP53 mutation, bruton's tyrosine kinase (BTK) inhibitor
Medical subject headings
Lymphoma, B-Cell

What participants receive

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

  • ibrutinib and TisagenlecleucelCombination product

    Single-arm study investigating combination of ibrutinib and Tisagenlecleucel treatment

Study groups in NCT04234061
Study groupRoleWhat they receive
SingleExperimentalibrutinib and Tisagenlecleucel
Receives: Combination Product: ibrutinib and Tisagenlecleucel

What is being measured

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

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

    Using the Lugano criteria

    Measured: 4 months after Tisagenlecleucel infusion using the Lugano criteria

Secondary outcomes (7)

  1. 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

    Through monitoring of the incidence, nature and severity of adverse events (graded according to NCI CTCAE v5.0), Serious Adverse Events, dose interruptions and dose reductions of ibrutinib

    Measured: 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

  2. Estimate objective response (OR) rate at day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel using Lugano criteria

    Using Lugano criteria

    Measured: day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel

  3. To estimate objective response (OR) rate at day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel by TP53 status

    Assessment of TP53 status

    Measured: day 28, month 4, 6, 9 and 12 following the infusion of Tisagenlecleucel by TP53 status

  4. To estimate Minimal Residual Disease (MRD) negative response rates by aggregate measure of peripheral blood/or bone marrow flow cytometry, PCR and ctDNA

    Measured through aggregate measure of peripheral blood/or bone marrow flow cytometry, PCR and ctDNA

    Measured: At day 28, months 4, 6, 9 and 12 following the infusion of Tisagenlecleucel

  5. To estimate progression-free survival

    According to Lugano criteria

    Measured: 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

  6. To estimate duration of response

    Using Lugano criteria

    Measured: 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

  7. To estimate overall survival

    By monitoring for patient death due to any cause

    Measured: 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

Timeline

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

  1. First posted21 Jan 2020
  2. Study start7 Apr 2020
  3. Primary completion1 Sep 2027 (estimated)
  4. Study completion1 Sep 2030 (estimated)

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
Model description
single arm
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04234061
Sponsor's protocol ID
19/008
Acronym
TARMAC
Status last verified
Nov 2024
First submitted
5 Jan 2020
Last updated
7 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37883795

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ibrutinib and Tisagenlecleucel in people with Mantle Cell Lymphoma Recurrent, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

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 31 inclusion and 31 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: under way, not looking for participants, as of the sponsor's last update on 7 Nov 2024. 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 Australia. 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?

This study is still under way. Results are not available in the source record yet.

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?

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). 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 NCT04234061, which also lists 1 linked publication.

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 7 Nov 2024.

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