Health TrialsbyHealthPanel

Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

ConditionMantle Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, San Francisco

About this trial

This phase II trial tests the safety and effectiveness of glofitamab given in combination with pirtobrutinib in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Obinutuzumab may also reduce the risk of immune-related conditions from treatment. Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the protein that signals cancer cells to multiply. Giving glofitamab in combination with pirtobrutinib may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years at the time of signing the informed consent form.

Have a life expectancy (in the opinion of the investigator) of at least 12 weeks.

Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%).

History of previously treated MCL meeting the following criteria: Relapsed after or failed to respond to at least one prior line of systemic therapy including anti-CD20 monoclonal antibody and alkylator-containing chemotherapy.

Disqualifiers

Pregnant, or intention of becoming pregnant during the study or within 18 months after treatment with obinutuzumab or 2 months after the last dose of glofitamab, or 3 months after treatment with tocilizumab, whichever is longer; and 1 month after the last dose of pirtobrutinib.

Participants should avoid chest-feeding until at least 1 week after discontinuing pirtobrutinib.

Participants who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor. NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome)

Any grade 3 or higher non-hematologic toxicity, except a major bleeding event or grade >= 3 arrhythmia which are exclusion criteria

Trial design

Design model

Single group

Treatments tested in this trial

  • Obinutuzumab

    Biological/Vaccine

    Given intravenously (IV)

  • Glofitamab

    Biological/Vaccine

    Given IV

  • Pirtobrutinib

    Drug

    Given Orally (PO)

  • Tumor Imaging

    Procedure/Surgery

    Undergo regular care imaging/scans

  • Biospecimen Collection

    Procedure/Surgery

    Blood and tissue samples

  • ClonoSeq Assay

    Device

    ClonoSEQ is an FDA-cleared, Clinical Laboratory Improvement Amendments of 1988 (CLIA)-validated measure used to determine minimal residual disease (MRD). This helps uncover how much, if any, cancer remains in your body during and after treatment.

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy and aspiration.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: Treatment (obinutuzumab, glofitamab, pirtobrutinib)Experimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

Percentage of participants with high grade, treatment-emergent adverse events (AEs)

The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. AEs and clinically significant laboratory abnormalities meeting grade 3 4 or 5 will be summarized by maximum intensity and relationship to study drug for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days.

Time frame
Approximately 2 weeks
2

Proportion of participants with Complete Response (CR)

CR will be defined as the proportion of treated participants who experience a CR per Lugano criteria among evaluable participants. The Lugano classification recommends the Deauville five-point scale for reporting response by Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT): (1) no uptake or no residual uptake (when used interim) (2) slight uptake, but below blood pool (mediastinum) (3) uptake above mediastinal, but below or equal to uptake in the liver (4) uptake slightly to moderately higher than liver (5) markedly increased uptake or any new lesion (on response evaluation) from cycle 5 Day 1 through the follow-up period up to 94 weeks.

Time frame
Up to 94 weeks
3

Proportion of participants with reported Cytokine-release syndrome (CRS)

The proportion of participants with a diagnosed incident of CRS for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.

Time frame
Approximately 2 weeks
4

Proportion of participants with immune effector cell-associated neurotoxicity syndrome (ICANS)

The proportion of participants with a diagnosed incident of ICANS for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.

Time frame
Approximately 2 weeks

Secondary outcomes

1

Median Progression-free survival (PFS)

PFS will be defined as the time that elapses between initiation of trial therapy and the earlier of the day of first documented disease progression or death from any cause. Progression is defined by Lugano criteria of (1) new or increased adenopathy; an individual node must be abnormal with: (a) longest transverse diameter (LDi) \>1.5 cm AND (2) splenic volume increase (3) new or larger non-measured lesions (4) recurrent previously resolved lesions (5) new extranodal lesion \>1 cm in any axis (new lesions \<1 cm in any axis are included if these are "unequivocally attributable" to lymphoma) (6) a new node \>1.5 cm in any axis . PFS will be summarized using Kaplan-Meier method.

Time frame
Up to 94 weeks
2

Median Overall Survival (OS)

OS will be defined as the time that elapses between the initiation of trial therapy and the date of death from any cause for all evaluable participants. OS will be summarized using Kaplan-Meier method.

Time frame
Up to 94 weeks
3

Objective Response Rate (ORR)

OR will be defined as the proportion of treated participants who experience an objective response (CR or partial response (PR) per Lugano criteria) among evaluable participants.

Time frame
Up to 94 weeks
4

Duration of response (DOR)

DOR will be defined as the time that elapses between the day of first documented response to trial therapy (CR or PR, whichever is first recorded) and subsequent disease progression.

Time frame
Up to 94 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, San Francisco

Lead sponsor

Eli Lilly and Company

Collaborator

Genentech, Inc.

Collaborator

Adaptive Biotechnologies

Collaborator

Source ClinicalTrials.gov
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