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The goal of this clinical trial is to evaluate the safety and response of combining Pirtobrutinib and Glofitimab in patients with relapsed MCL. The main question it aims to answer are:
Pirtobrutinib will be given to all participants as an oral tablet for the duration of the entire study. Participants will receive other treatment in 3 phases:
Treatment Ramp-Up
Fixed course combination phase: Treatment with Glofitamab by IV
Maintenance phase: Glofitamab is discontinued. 200mg oral daily
Full description
The goal of this clinical trial is to evaluate the safety and response of combination Pirtobrutinib and Glofitimab in patients with relapsed/refractory MCL. The main question it aims to answer are:
Participants will receive treatment based on 21 day cycles. This study design involves 3 phases:
Treatment Ramp-Up
i. Dose level 1 (14 days):
Fixed course combination phase: Cycles 3-12 (21 days per cycle): 30mg of Glofitamab by IV on day 1
Maintenance phase: Cycles 13+ (21 days per cycle): Glofitamab discontinued. 200mg oral daily
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Ages 18 years old or above
A confirmed diagnosis of MCL according to World Health Organization (2016) criteria
At least one site of measurable disease not previously irradiated (defined as at least one bi-dimensionally measurable nodal lesion of greater than or equal to 1.5cm in longest dimension)
Life expectancy (in the opinion of the investigator) of greater than or equal to 18 weeks
Prior therapy with a BTK inhibitor alone or in combination and:
Prior TRAEs must have recovered to Grade 1 or less with the exception of alopecia, peripheral neuropathy and lymphopenia.
ECOG 0-2
Adequate washout of prior therapies:
Ability to take oral medications
Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
Willingness of men and women of reproductive potential to observe conventional and highly effective and acceptable birth control methods for the duration of treatment and for six months following the last dose of study treatment
Women of childbearing potential must have a negative serum pregnancy test within seven days of enrolment
Adequate coagulation, defined as aPTT and PT not greater than 1.5xULN, unless laboratory abnormality is explained by concomitant anticoagulant medication, a lupus anticoagulant, or a factor deficiency not associated with an increased bleeding risk, as determined by the investigator.
Adequate liver function:
Adequate renal function
Adequate haematological parameters
Sufficient archival tissue is available for central review or after discussion with the CPI
Exclusion criteria
Inability to comply with protocol mandated hospitalisations
For patients enrolling on the safety cohort, a history of allogeneic transplantation within 12 months of enrolment or ongoing chronic GVHD or immunosuppressive therapy.
Autologous SCT or CAR-T therapy within 6 weeks of enrolment
Active central nervous system involvement with MCL
Prior treatment with pirtobrutinib or demonstrated refractoriness to a CD20xCD3 bispecific antibody.
Have a known severe hypersensitivity to any of the excipients of pirtobrutinib, glofitamab, tocilizumab or obinutuzumab.
History of stroke or intracranial haemorrhage within six months of enrolment.
Live vaccination within 28 days of enrolment.
Major surgery or significant traumatic injury within 28 days of study treatment or the anticipation of major surgery during study treatment (surgical procedures for the diagnosis of lymphoma such as lymph node resection/ laparoscopy are allowed provided patient is considered fit for treatment as judged by investigator)
Significant cardiovascular disease defined as:
Prolongation of the QT interval corrected for heart rate (QTcF) greater than 470 msec on at least 2/3 consecutive electrocardiograms (ECGs), and mean QTcF greater than 470 msec on all 3 ECGs, during Screening. QTcF is calculated using Fridericia's Formula (QTcF): QTcF euqal to QT/(RR0.33) Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switching to another drug not known to be associated with QTcF prolongation. Correction for underlying bundle branch block (BBB) allowed. Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias
Known human immunodeficiency virus (HIV) infection
Known active HBV or HCV infection based on criteria below:
Known active CMV infection. Unknown or negative status are eligible.
Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment.
Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of pirtobrutinib.
Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection, or other clinically significant active disease process which in the opinion of the investigator and medical monitor may pose a risk for patient participation.
Active uncontrolled auto-immune cytopenia (e.g., AIHA, ITP) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrolment to maintain adequate blood counts, unless auto-immune cytopenias are secondary to MCL
Active second malignancy unless in remission and with life expectancy greater than 2 years.
Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors.
Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
Primary purpose
Allocation
Interventional model
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42 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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