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A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure.

RecruitingPhase 2Ages 18 Years - anyAllAustralasian Leukaemia and Lymphoma Group
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In plain words

What the trial is, and whether it could suit you

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: * Will additive and synergistic effects be observed when using a combination of glofitamab and pirtobrutinib? * Will this combination be safe and lead to high complete- and remission rates with no residual disease? 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: 1. Treatment Ramp-Up 1. Treatment with Obinutuzumab by Intravenous (IV) 2. An initial dose level of Glofitamab will evaluate step-up dosing. If excessive adverse events are observed, a lower initial dose will be used. 2. Fixed course combination phase: Treatment with Glofitamab by IV 3. Maintenance phase: Glofitamab is discontinu

Sign in to get the eligibility rules as simple questions to take to your doctor.

๐Ÿ“‹ Eligibility rules (as published)
Inclusion Criteria: 1. Ages 18 years old or above 2. A confirmed diagnosis of MCL according to World Health Organization (2016) criteria 3. 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) 4. Life expectancy (in the opinion of the investigator) of greater than or equal to 18 weeks 5. Prior therapy with a BTK inhibitor alone or in combination and: 1. Progression or relapse post BTK inhibitor or 2. Failed to achieve PR following 12 weeks of BTK inhibitor therapy 6. Prior TRAEs must have recovered to Grade 1 or less with the exception of alopecia, peripheral neuropathy and lymphopenia. 7. ECOG 0-2 8. Adequate washout of prior therapies: 1. Broad field radiation (greater than or equal to 30% of the bone marrow or whole brain radiotherapy) must be completed 14 days prior to study treatment 2. Palliative limited field radiation must be completed 7 days prior to study treatment. 3. Targeted agents, investigational agents, therapeutic monoclonal antibodies/antibody drug conjugates or cytotoxic chemotherapy must be completed 5 half-lives or 2 weeks (whichever is shorter) prior to study treatment (except for BTK inhibitors which may be continued until 1 day prior to planned first therapy with pirtobrutinib) 4. Steroids (prednisolone less than or equal to 100mg daily or equivalent for up to 14 days are permitted during screening for control of lymphoma related symptoms 9. Ability to take oral medications 10. Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol. 11. 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 12. Women of childbearing potential must have a negative serum pregnancy test within seven days of enrolment 13. 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. 14. Adequate liver function: * ALT and AST less than or equal to 3X ULN, or less than or equal to 5X ULN if documented liver involvement * Total bilirubin less than or equal to 1.5X ULN or less than or equal to 5X ULN if documented liver involvement and/or Gilbert's Disease 15. Adequate renal function \- Creatinine clearance greater than or equal to 30mls/minute according to Cockroft-Gault formula 16. Adequate haematological parameters * Haemoglobin greater than or equal to 80g/L (transfusion support permitted) * Absolute neutrophil count greater than or equal to 1.0x10\^9/L (May be G-CSF supported) * Platelets greater than or equal to 75 X 10\^9/L. OR platelets greater than or equal to 50 X 10\^9/L if documented marrow involvement or splenomegaly (must be platelet transfusion independent for 7 days prior to first dose of obinutuzumab 17. Sufficient archival tissue is available for central review or after discussion with the CPI Exclusion Criteria: 1. Inability to comply with protocol mandated hospitalisations 2. For patients enrolling on the safety cohort, a history of allogeneic transplantation within 12 months of enrolment or ongoing chronic GVHD or immunosuppressive therapy. 3. Autologous SCT or CAR-T therapy within 6 weeks of enrolment 4. Active central nervous system involvement with MCL 5. Prior treatment with pirtobrutinib or demonstrated refractoriness to a CD20xCD3 bispecific antibody. 6. Have a known severe hypersensitivity to any of the excipients of pirtobrutinib, glofitamab, tocilizumab or obinutuzumab. 7. History of stroke or intracranial haemorrhage within six months of enrolment. 8. Live vaccination within 28 days of enrolment. 9. 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) 10. Significant cardiovascular disease defined as: 1. Unstable angina or acute coronary syndrome within 2 months of registration 2. History of myocardial infarction within 3 months prior to registration 3. Documented LVEF by any method of = 40% during screening 4. Grade 3 or higher NYHA functional classification system of heart failure 5. Uncontrolled or symptomatic arrhythmias 11. 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 12. Known human immunodeficiency virus (HIV) infection 13. Known active HBV or HCV infection based on criteria below: 1. HBV: Patients with positive HbsAg are excluded. Patients with positive hepatitis B core antibody antiHBc and negative HbsAg require negative hepatitis B PCR before enrolment and must be treated with antiviral therapy. Patients who are hepatitis B PCR positive will be excluded. 2. HCV: If positive hepatitis C antibody, patient will need
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What it tests

  • Glofitamab
  • Pirtobrutinib
  • Obinutuzumab
  • Tocilizumab
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Where

2 sites
Peter MacCallum Cancer Centre
Parkville, Australia
Sir Charles Gairdener
Nedlands, Australia
๐Ÿค Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible โ€” always decide together with your own doctor.
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