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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05833763




Registration number
NCT05833763
Ethics application status
Date submitted
26/03/2023
Date registered
27/04/2023

Titles & IDs
Public title
A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure.
Scientific title
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
Secondary ID [1] 0 0
NHL37
Universal Trial Number (UTN)
Trial acronym
GOlDiLOX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mantle Cell Lymphoma 0 0
Mantle Cell Lymphoma Refractory 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Glofitamab
Treatment: Drugs - Pirtobrutinib
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Tocilizumab

Experimental: Study Treatment - This study design involves 3 phases:

1. Treatment Ramp-Up

1. Pre-Phase (7 days): Obinutuzumab (1000mg) will be administered intravenously (IV) on D-7 and a second dose administered between Day 6 and Day 1.
2. Cycle 1: An initial dose level of Glofitamab will evaluate step-up dosing. If excessive dose-limiting toxicity is observed, including cytokine release syndrome (CRS), a lower initial dose of 1.25mg of glofitamab will be evaluated at "dose level -1".

i. Dose level 1 (14 days):
* 2.5mg Glofitamab by IV on Day 1
* 10mg Glofitamab by IV on Day 8 ii. Dose level -1 (21 days):
* 1.25mg Glofitamab by IV on Day 2
* 2.5mg Glofitamab by IV on Day 8
* 10mg Glofitamab by IV on Day 15 c. Cycle 2 (21 days): 30mg Glofitamab by IV on Day 1
2. Fixed course combination phase: Cycles 3-12 (21 days per cycle): 30mg of Glofitamab by IV on day 1
3. Maintenance phase: Cycles 13+ (21 days per cycle): Glofitamab discontinued. 200mg oral daily


Treatment: Drugs: Glofitamab
Glofitamab is provided as liquid concentrate for IV infusion. Each vial contains 10mg of glofitamab.

Treatment: Drugs: Pirtobrutinib
Pirtobrutinib is supplied as immediate release film-coated tablets containing 50 mg, or 100 mg of active compound. Tablets are supplied in labelled, HDPE bottles and sealed with child-resistant closures.

Treatment: Drugs: Obinutuzumab
Obinutuzumab is provided as a single dose 1000 mg liquid concentrate for infusion containing of 25 mg/mL obinutuzumab.

Treatment: Drugs: Tocilizumab
Tocilizumab is provided as a liquid concentrate for IV infusion. Each vial contains 200mg/10mL concentrate solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the efficacy of combination Pirtobrutinib and Glofitmab in patients with relapsed/refractory MCL and prior BTK inhibitor exposure.
Timepoint [1] 0 0
Following six cycles (or approximately 18 weeks following first treatment). Cycle 1 is 14 days in duration and cycles 2 to 6 are 21 days in duration.
Secondary outcome [1] 0 0
Complete response rate using the Lugano Criteria for response assessment at end of 12 cycles of Glofitamab
Timepoint [1] 0 0
When all patients have completed 12 cycles of Glofitamab. Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Secondary outcome [2] 0 0
Assessment of adverse events (eg. fatigue, diarrhoea, confusion, nausea, constipation, anaemia, dyspnoea)
Timepoint [2] 0 0
Analysis of the adverse events will be completed in line with the primary and secondary endpoints; When all patients have completed 6 cycles of protocol treatment, when all patients have completed 12 cycles of treatment.
Secondary outcome [3] 0 0
Overall response rates (complete or partial response) to combination therapy.
Timepoint [3] 0 0
At the end of combination therapy (cycle 12).Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Secondary outcome [4] 0 0
Overall response rates
Timepoint [4] 0 0
At the end of combination therapy (cycle 12). Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Secondary outcome [5] 0 0
Absence of minimal residual disease (MRD)
Timepoint [5] 0 0
Following six cycles and 12 cycles of combination treatment. Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Secondary outcome [6] 0 0
Progression-free survival (PFS)
Timepoint [6] 0 0
Progression is measured from the date of registration to the date of first progression at any site or date of death due to any cause. Patients will be followed assessed until the last patient registered completes 5 years of follow up.
Secondary outcome [7] 0 0
Duration of response
Timepoint [7] 0 0
Patient's will be followed assessed until the last patient registered completes 5 years of follow up.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 to have a negative hepatitis C RNA before enrolment. Patients who are hepatitis C RNA positive will be excluded.
14. Known active CMV infection. Unknown or negative status are eligible.
15. Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment.
16. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of pirtobrutinib.
17. 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.
18. 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
19. Active second malignancy unless in remission and with life expectancy greater than 2 years.
20. Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors.
21. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2037
Actual
Sample size
Target
42
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Parkville
Recruitment hospital [2] 0 0
Sir Charles Gairdener - Nedlands
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment postcode(s) [2] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Leukaemia and Lymphoma Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be shared publicly. Aggregate patient data and final results will be presented in the final report.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05833763