Actively Recruiting
An Open-label, Single-arm, Phase 2 Trial of GlOfitamab and Pirtobrutinib (LOXo-305) in Patients With Mantle Cell Lymphoma and Prior Exposure to a BTK Inhibitor
Led by Australasian Leukaemia and Lymphoma Group · Updated on 2024-01-08
42
Participants Needed
2
Research Sites
260 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This trial studies patients with relapsed or refractory Mantle Cell Lymphoma (MCL) who have previously been treated with BTK inhibitors. Researchers are evaluating the safety and response of combining two drugs: Pirtobrutinib and Glofitamab. The main goals are to see if the combination produces additive or synergistic effects and achieves high rates of complete remission with no residual disease. Participants take Pirtobrutinib as an oral tablet throughout the study. Treatment occurs in three phases: an initial ramp-up phase with intravenous Obinutuzumab and step-up dosing of Glofitamab; a fixed course combination phase with repeated Glofitamab infusions over cycles 3 to 12; and finally, a maintenance phase where Glofitamab is stopped and only daily oral Pirtobrutinib is continued. During the study, participants undergo evaluations after six cycles (approximately 18 weeks) and after twelve cycles of treatment. Researchers assess efficacy using response criteria and measure minimal residual disease. Safety is monitored by tracking adverse events and laboratory tests. Patients will be followed for up to five years to evaluate progression-free survival and duration of response.
CONDITIONS
Brief Title
A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure.
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Confirmed diagnosis of Mantle Cell Lymphoma (MCL) according to WHO 2016 criteria
- At least one measurable disease site not previously irradiated (lesion ≥1.5 cm)
- Life expectancy of at least 18 weeks
- Prior treatment with a BTK inhibitor and progression, relapse, or failure to achieve partial response after 12 weeks
- Recovery from prior treatment-related adverse events to Grade 1 or less (except alopecia, peripheral neuropathy, lymphopenia)
- ECOG performance status 0-2
- Completion of prior therapies with required washout periods
- Ability to take oral medications
- Signed informed consent and willingness to comply with study requirements
- Use of effective birth control during treatment and for 6 months after
- Negative pregnancy test for women of childbearing potential
- Adequate coagulation, liver, kidney, and blood function
- Sufficient archival tissue available for review
You will not qualify if you...
- Inability to comply with required hospitalizations
- Allogeneic transplant within 12 months or ongoing chronic GVHD or immunosuppression for safety cohort
- Autologous stem cell transplant or CAR-T therapy within 6 weeks
- Active central nervous system involvement with MCL
- Prior treatment with pirtobrutinib or resistance to CD20xCD3 bispecific antibodies
- Severe allergy to study drugs or their components
- Stroke or brain bleeding within 6 months
- Live vaccination within 28 days
- Major surgery or trauma within 28 days or planned during study
- Significant cardiovascular disease or uncontrolled arrhythmias
- Prolonged QT interval on ECG
- Known HIV infection
- Active hepatitis B or C infection
- Active CMV infection
- Pregnancy, breastfeeding, or plans to breastfeed
- Significant gastrointestinal absorption issues
- Other uncontrolled active diseases or infections
- Active autoimmune cytopenia requiring recent new or increased therapy unless related to MCL
- Active second cancer unless in remission with life expectancy >2 years
- Current treatment with strong CYP3A4 or P-gp inhibitors or inducers
- Requirement for therapeutic anticoagulation with warfarin or vitamin K antagonists
AI-Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 49 days depending on dose level (7 days pre-phase plus 14 to 21 days for cycle 1 and 21 days for cycle 2)
Participants receive obinutuzumab infusions during a 7-day pre-phase followed by step-up dosing of glofitamab in cycle 1, and then receive glofitamab in cycle 2.
Multiple visits for infusions during pre-phase and cycles 1 and 2
Duration - Approximately 189 days (9 cycles of 21 days each)
Participants receive cycles 3 to 12 of glofitamab infusions combined with pirtobrutinib treatment.
9 infusion visits, one per cycle
Duration - Ongoing 21-day cycles starting from cycle 13 until study end or discontinuation
Participants discontinue glofitamab and continue daily oral pirtobrutinib as maintenance treatment.
Daily oral medication with periodic study visits
Trial Site Locations
Total: 2 locations
1
Peter MacCallum Cancer Centre
Parkville, Victoria, Australia, 3050
Actively Recruiting
2
Sir Charles Gairdener
Nedlands, Western Australia, Australia, 6009
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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