Trial Title:
Glofitamab Plus Ibrutinib With Obinutuzumab for the Treatment of Patients With Mantle Cell Lymphoma
NCT ID:
NCT06357676
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Antineoplastic Agents, Immunological
Obinutuzumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Ibrutinib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan or FDG PET/CT
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo echocardiography
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
EC
Intervention type:
Procedure
Intervention name:
FDG-Positron Emission Tomography
Description:
Undergo FDG PET/CT
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
FDG
Other name:
FDG-PET
Other name:
FDG-PET Imaging
Intervention type:
Biological
Intervention name:
Glofitamab
Description:
Given IV
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody RO7082859
Other name:
RO 7082859
Other name:
RO7082859
Intervention type:
Drug
Intervention name:
Ibrutinib
Description:
Given PO
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
BTK Inhibitor PCI-32765
Other name:
CRA-032765
Other name:
Imbruvica
Other name:
PCI-32765
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Obinutuzumab
Description:
Given IV
Arm group label:
Treatment (glofitamab, ibrutinib, obinutuzumab)
Other name:
Anti-CD20 Monoclonal Antibody R7159
Other name:
GA-101
Other name:
GA101
Other name:
Gazyva
Other name:
huMAB(CD20)
Other name:
R7159
Other name:
RO 5072759
Other name:
RO-5072759
Other name:
RO5072759
Summary:
This phase IB/II trial tests the safety, side effects and effectiveness of glofitamab
plus ibrutinib with obinutuzumab for the treatment of patients with mantle cell lymphoma
(MCL). Glofitamab is in a class of medications called bispecific monoclonal antibodies.
It works by killing cancer cells. A monoclonal antibody is a type of protein that can
bind to certain targets in the body, such as molecules that cause the body to make an
immune response (antigens). In the body, glofitamab binds to a receptor called CD3 on
T-cells (a type of immune cells) and a receptor called CD20 on B-cells, a receptor that
is often over-expressed on the surface of cancerous B-cells. When glofitamab binds to CD3
and CD20 receptors, it causes an immune response against the CD20-expressing cancerous
B-cells. Ibrutinib is in a class of medications called kinase inhibitors. It works by
blocking the action of the abnormal protein that signals cancer cells to multiply. This
helps stop the spread of cancer cells. Obinutuzumab is a monoclonal antibody that may
interfere with the ability of cancer cells to grow and spread. Glofitamab plus ibrutinib
with obinutuzumab may be safe tolerable and/or effective in treating patients with MCL.
Detailed description:
PRIMARY OBJECTIVES:
I. Determine the safety and tolerability of treatment with glofitamab and ibrutinib
(GLIB) for previously untreated MCL in patients with high risk or age ≥ 65 yrs. (Phase
Ib) I. Determine the efficacy of treatment with GLIB for previously untreated MCL in
patients with high risk or age ≥ 65 yrs. (Phase II)
SECONDARY OBJECTIVES:
I. Assess the overall acute toxicity and tolerability of treatment with GLIB. II. Assess
the preliminary efficacy of treatment with GLIB based on clinical response.
III. Assess survival in the absence of progressive disease, recurrence of disease, or
death due to any cause after treatment with GLIB.
IV. Assess the duration of clinical response and complete response to treatment with
GLIB.
EXPLORATORY OBJECTIVES:
I. Evaluate response to treatment evaluated as minimal residual disease (MRD). II.
Evaluate the differential impact of treatment on T cell populations in the tumor
microenvironment.
OUTLINE:
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21 of cycles 1-17.
Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or
unacceptable toxicity. Patients receive glofitamab intravenously (IV) over 2-4 hours on
days 8 and 15 of cycle 2 and then on day 1 of cycles 3-13. Cycles repeat every 21 days
for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients also receive obinutuzumab IV over 4 hours at least 7 days and 24 hours prior to
first dose of glofitamab. Additionally, patients undergo echocardiography during
screening, bone marrow biopsy on study, and computed tomography (CT) scans,
fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT)
scans or magnetic resonance imaging (MRI), and blood sample collection throughout the
study.
After completion of study treatments, patients are followed up every 3 months for up to 2
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Ability to understand the purpose and risks of the study and to provide signed
informed consent
- Pathologically confirmed MCL, with documentation of chromosome translocation
t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other
relevant markers (e.g., CD5, CD19, CD20, PAX5)
- Age 18-64 with one or more of the following poor risk features defined as:
- High risk mutational variants including p53 mutation and/or17p deletion;
- Blastoid or pleomorphic phenotype;
- Complex karyotype with ≥ 3 abnormalities (in addition to t(11,14)) on routine
karyotyping;
- Ki67 > 30%;
- sMIPI > 6.2; and/or
- p53 expression on immunohistochemistry (IHC), defined as > 20%
- Age ≥ 65. For this population, no poor risk features are required to be eligible
- No prior systemic anticancer therapies for MCL
- Presence of radiologically measurable lymphadenopathy and/or extranodal lymphoid
malignancy
- Able to provide biosamples for MRD testing and pathology. If fresh tissue is not
available, archival samples can be used at the discretion of the investigator
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L independent of growth factor support
- Platelets ≥ 1.0 × 10^9/L (≥ 0.5 × 10^9/L if bone marrow [BM] involvement),
independent of transfusion support in either situation
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper
limit of normal (ULN)
- Total bilirubin ≤ 1.5 × ULN (unless due to Gilbert's syndrome or of non hepatic
origin)
- Serum creatinine ≤ ULN; or estimated creatinine clearance ≥ 50 mL/min by Cockroft
Gault method or other approved methods, at the discretion of the investigator
- Undetectable hepatitis B virus (HBV) surface antigen (sAg) serology. Confirmed by
polymerase chain reaction (PCR) for HBV deoxyribonucleic acid (DNA) if results are
disputable
- Undetectable hepatitis C virus (HCV) antigen serology. Confirmed by PCR for HCV
ribonucleic acid (RNA) if results are disputable
- Undetectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) based on
PCR testing within 7 days of enrollment
- Undetectable HIV based on serology. Enrollment will be considered if HIV is
controlled with treatment (i.e., undetectable viral load for 6 months prior and the
CD4 counts is ≥ 200/µL). Such patients must be willing to modify HIV therapy while
on-treatment and during applicable wash-out periods, as needed, to address drug-drug
interactions
- Willing and able to participate in all required evaluations and procedures in this
protocol including swallowing capsules without difficulty
- Persons of childbearing potential (PCBP): Persons of childbearing potential must
have a negative serum (beta-human chorionic gonadotropin [b-hCG]) or urine pregnancy
test at Screening and be willing to use approved contraception while on treatment
and for the longest following, applicable time period: 18 months after the last dose
of obinutuzumab, 2 months after the last dose of glofitamab, 3 months for
tocilizumab, or 1 month after the last dose of ibrutinib. Women who are pregnant or
breastfeeding are ineligible for this study
- Persons that produce viable sperm: Willingness to use approved contraception while
on-treatment and for the longest applicable time period following: 6 months after
the last dose of obinutuzumab or 2 months after the last dose of glofitamab,
tocilizumab, or ibrutinib
- Willingness to not breastfeed or donate ova or sperm: If obinutuzumab was the last
study drug received, the participant must wait for 6 months. Otherwise, patients
must agree to wait 3 months for sperm and 1 month for ova donations (and to
breastfeed) after the last dose other study drugs
- The effects of GLIB on the developing human fetus are unknown. Should a participant
or participant's sexual partner become pregnant or suspect a pregnancy while
participating in this study, the individual should inform their treating physician
immediately
Exclusion Criteria:
- Previous MCL-directed treatment. Treatment with corticosteroids (up to 20 mg
dexamethasone or equivalent daily) is allowed prior to and during the screening
period for patients with aggressive clinical behavior. All steroids used for disease
control must be discontinued within 7 days after starting study treatment
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined
by the New York Heart Association Functional Classification
- History of prior malignancy except for the following:
- Malignancy treated with curative intent and with no evidence of active disease
present for more than 2 years before screening and felt to be at low risk for
recurrence by treating physician
- Persons with low grade prostate cancer on a watch and wait strategy are
eligible
- Adequately treated lentigo maligna melanoma without current evidence of disease
or adequately controlled nonmelanomatous skin cancer
- Adequately treated carcinoma in situ without current evidence of disease
- Ongoing hormonal therapy alone for prior malignancy is allowed
- Concurrent use of cytotoxic chemotherapy; radiotherapy; immunotherapy; hormone
therapy (other than contraceptives, hormone-replacement therapy, or megestrol
acetate); and biologic agents (other than hematopoietic growth factors, if
clinically indicated and used in accordance with manufacture and Investigator
recommendations), unless approved by the investigator
- Received systemic immunosuppressive medications (e.g., cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents)
within 2 weeks prior to Gpt infusion with the exceptions of corticosteroid ≤ 25
mg/day prednisone or equivalent and inhaled and topical steroids
- Known history of hypersensitivity to
- Humanized or murine monoclonal antibodies or products
- A CD3 and / or CD20 antibody
- Glofitamab
- Ibrutinib
- Tocilizumab
- Current or past history of epilepsy, central nervous system (CNS) vasculitis, and
neurodegenerative disease
- History of autoimmune disease (e.g., myocarditis, pneumonitis, myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a remote
history of, or well controlled, autoimmune disease may be eligible to enroll after
consultation with the primary investigator
- History of bleeding risks:
- Stroke, transient ischaemic attack (TIA),or intracranial hemorrhage within 2
years of first dose of study drug given no remaining neurological deficits
- Known bleeding diathesis (e.g., hemophilia or von Willebrand disease)
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months
prior to cycle 1 day 1 (C1D1)
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (e.g., phenprocoumon) within 7 days of first dose of C1D1
- Requires treatment with a strong CYP3A inhibitor/inducer, except for the following:
- A plan to modify concurrent CYP3A inhibitor/inducer and/or wash-out periods
prior to C1D1
- Topical ketoconazole: Based on its low overall bioavailability, there are no
restrictions
- Concurrent participation in another therapeutic clinical trial
- History of confirmed progressive multifocal leukoencephalopathy (PML) or
lymphomatous involvement of the CNS
- Known or suspected history of hemophagocytic lymphohistiocystosis (HLH)
- Evidence of ongoing acute or systemic infections (bacterial, fungal, or viral), or
any major episode of infection requiring hospitalization or treatment with IV
antibiotics (for IV antibiotics this pertains to completion of last course of
antibiotic treatment) within 4 weeks of dosing, except localized fungal infections
of skin or nails. Subjects may be receiving prophylactic antiviral or antibacterial
therapies at the discretion of the investigator
- Receipt of live vaccine within 4 weeks of enrollment or during study treatment
period
- Any life-threatening illness, medical condition, or organ system dysfunction which,
in the investigator's opinion, could compromise the subject's safety, interfere with
the absorption or metabolism of ibrutinib capsules, or put the study outcomes at
undue risk
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
OHSU Knight Cancer Institute
Address:
City:
Portland
Zip:
97239
Country:
United States
Contact:
Last name:
Knight Cancer Clinical Trials Hotline
Phone:
503-494-1080
Email:
trials@ohsu.edu
Investigator:
Last name:
Stephen E. Spurgeon
Email:
Principal Investigator
Start date:
May 1, 2024
Completion date:
May 1, 2029
Lead sponsor:
Agency:
OHSU Knight Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Oregon Health and Science University
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
OHSU Knight Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06357676
