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Mantle Cell LymphomaPhase 2GOlDiLOXNCT05833763

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

A Phase 2 study testing Glofitamab, Pirtobrutinib and Obinutuzumab in people with Mantle Cell Lymphoma and Mantle Cell Lymphoma Refractory, run by Australasian Leukaemia and Lymphoma Group at 2 sites in Australia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Glofitamab, Pirtobrutinib and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
2 sitesAustralia
Study dates
12 Oct 2023to Apr 2037
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

  • 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:
  • Progression or relapse post BTK inhibitor or
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  • Failed to achieve PR following 12 weeks of BTK inhibitor therapy
  • 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:
  • 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
  • Palliative limited field radiation must be completed 7 days prior to study treatment.
  • 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)
  • 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
  • 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:
  • 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
  • Adequate renal function
  • Creatinine clearance greater than or equal to 30mls/minute according to Cockroft-Gault formula
  • 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
  • Sufficient archival tissue is available for central review or after discussion with the CPI

Who cannot join

  • 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.
Show all 28Show fewer
  • 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:
  • Unstable angina or acute coronary syndrome within 2 months of registration
  • History of myocardial infarction within 3 months prior to registration
  • Documented LVEF by any method of = 40% during screening
  • Grade 3 or higher NYHA functional classification system of heart failure
  • Uncontrolled or symptomatic arrhythmias
  • 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:
  • 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.
  • 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.
  • 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.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Australia2 sites, 2 recruiting

  • Sir Charles Gairdener

    Nedlands, Western Australia, 6009

    Naomi Sprigg, 07 63833453, nhl37@allg.org.au

    Chan Cheah

    Recruiting

  • Peter MacCallum Cancer Centre

    Parkville, Victoria, 3050

    Naomi Sprigg, 03 83739709, nhl37@allg.org.au

    Michhael Dickinson

    Recruiting

Other trials in Australia

About this study

Official 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

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?
Read more

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
  2. Treatment with Obinutuzumab by Intravenous (IV)
  3. An initial dose level of Glofitamab will evaluate step-up dosing. If excessive adverse events are observed, a lower initial dose will be used.
  4. Fixed course combination phase: Treatment with Glofitamab by IV
  5. Maintenance phase: Glofitamab is discontinued. 200mg oral daily
Read the detailed 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:

  • 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 MRD-negative remission rates?

Participants will receive treatment based on 21 day cycles. This study design involves 3 phases:

  1. Treatment Ramp-Up
  2. 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.
  3. 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".
  4. 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
  1. Fixed course combination phase: Cycles 3-12 (21 days per cycle): 30mg of Glofitamab by IV on day 1
  2. Maintenance phase: Cycles 13+ (21 days per cycle): Glofitamab discontinued. 200mg oral daily
Being tested
Glofitamab, Pirtobrutinib, Obinutuzumab, Tocilizumab
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

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

  • GlofitamabDrug

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

  • PirtobrutinibDrug

    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.

  • ObinutuzumabDrug

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

  • TocilizumabDrug

    Tocilizumab is provided as a liquid concentrate for IV infusion. Each vial contains 200mg/10mL concentrate solution

Study groups in NCT05833763
Study groupRoleWhat they receive
Study TreatmentExperimentalThis 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
Receives: Drug: Glofitamab; Drug: Pirtobrutinib; Drug: Obinutuzumab; Drug: Tocilizumab

What is being measured

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

  1. To evaluate the efficacy of combination Pirtobrutinib and Glofitmab in patients with relapsed/refractory MCL and prior BTK inhibitor exposure.

    Determined by the complete response (CR) rate according to Lugano criteria

    Measured: 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 outcomes (7)

  1. Complete response rate using the Lugano Criteria for response assessment at end of 12 cycles of Glofitamab

    Using the Lugano Criteria for response assessment

    Measured: 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.

  2. Assessment of adverse events (eg. fatigue, diarrhoea, confusion, nausea, constipation, anaemia, dyspnoea)

    Incidence, nature and severity of adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

    Measured: 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.

  3. Overall response rates (complete or partial response) to combination therapy.

    Using the Lugano criteria

    Measured: 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.

  4. Overall response rates

    Using the Lugano criteria

    Measured: 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.

  5. Absence of minimal residual disease (MRD)

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

    Measured: 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.

  6. Progression-free survival (PFS)

    Determined based on the modified Lugano criteria.

    Measured: 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.

  7. Duration of response

    Defined as the time from registration to date of death from any cause. Patients who have not died by the study close-out date will be censored at their last visit. Patients who are lost to follow-up before the close-out date and who are not known to have died will be censored at the date they were last known to be alive

    Measured: Patient's will be followed assessed until the last patient registered completes 5 years of follow up.

Timeline

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

  1. First posted27 Apr 2023
  2. Study start12 Oct 2023
  3. Primary completionApr 2032 (estimated)
  4. Study completionApr 2037 (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
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05833763
Sponsor's protocol ID
NHL37
Acronym
GOlDiLOX
Status last verified
Jan 2024
First submitted
26 Mar 2023
Last updated
8 Jan 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Individual patient data will not be shared publicly. Aggregate patient data and final results will be presented in the final report.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Glofitamab, Pirtobrutinib and Obinutuzumab in people with Mantle Cell Lymphoma and Mantle Cell Lymphoma Refractory, run by Australasian Leukaemia and Lymphoma Group at 2 sites 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 29 inclusion and 28 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: looking for participants now, as of the sponsor's last update on 8 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the efficacy of combination Pirtobrutinib and Glofitmab in patients with relapsed/refractory MCL and prior BTK inhibitor exposure. (time frame: 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.). 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 NCT05833763.

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 8 Jan 2024.

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