A Phase 2 Study of Glofitamab With Acalabrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma
This phase II trial studies the side effects of acalabrutinib, obinutuzumab, and glofitamab and how well they work together for 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). Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. 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). Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Glofitamab is a class of medications called bispecific antibodies. Bispecific antibodies are designed to simultaneously bind to T cells and cancer cell antigens, leading to T-cell activation, proliferation, and cancer cell death. Giving acalabrutinib, obinutuzumab, and glofitamab together may be a safe and effective treatment for patients with relapsed or refractory mantle cell lymphoma.
• Documented informed consent of the participant and/or legally authorized representative
• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from diagnostic tumor biopsies
‣ If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Histologically confirmed diagnosis of mantle cell lymphoma according to the World Health Organization (WHO) classification
‣ Relapsed or refractory disease after at least 1 prior line of systemic therapy
⁃ Relapse must have been confirmed histologically with hematopathology review at the participating institution. Exceptions may be granted with study PI approval
• Tumor must be positive for CD20 by immunohistochemistry or flow cytometry after the most recent therapy
• Active disease requiring treatment per treating physician's decision
• Radiographically measurable disease by Lugano criteria (e.g., one or more nodal sites of disease \>= 1.5 cm and/or extranodal sites of disease \>= 1.0 cm in longest dimension)
‣ If measurable bone marrow involvement or circulating disease has been confirmed in the absence of radiographically measurable disease, exceptions may be granted with study PI approval
• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy
• Without bone marrow involvement: Absolute neutrophil count (ANC) \>= 1,000/mm\^3 With bone marrow involvement: No minimal requirement
‣ NOTE: Growth factor is not permitted within 7 days prior to screening unless cytopenia is secondary to disease involvement.
• Without bone marrow involvement: Platelets \>= 75,000/mm\^3 With bone marrow involvement: Platelets \>= 30,000/mm\^3
‣ NOTE: Platelet transfusions are not permitted within 7 days prior to screening unless cytopenia is secondary to disease involvement
• Hemoglobin \>= 8 g/dL unless anemia is secondary to disease involvement
‣ NOTE: Erythropoietin and/or red blood cell transfusions are not permitted within 7 days prior to screening.
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (If hepatic involvement by lymphoma, or Gilbert's disease: =\< 3X ULN)
• Aspartate aminotransferase (AST) =\< 2.5 x ULN (If hepatic involvement by lymphoma: AST =\< 5 x ULN)
• Alanine aminotransferase (ALT) =\< 2.5 x ULN (If hepatic involvement by lymphoma: ALT =\< 5 x ULN)
• Normal creatinine (Cr) level per local laboratory reference range or creatinine clearance of \>= 50mL/min per 24 hour urine test or the Cockcroft-Gault formula
• If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =\< 1.5 x ULN If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
• If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
• Left ventricular ejection fraction (LVEF) \>= 40%
• Oxygen (O2) saturation \>= 92% on room air
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
‣ NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females of childbearing potential\* to abstain from heterosexual intercourse or use two adequate methods of birth control, including at least one method with a failure rate of \< 1% per year, during the treatment period until at least 7 days after the final dose of acalabrutinib; at least 2 months after the final dose glofitamab; at least 18 months after the dose of obinutuzumab; and at least 4 months after the last dose of tocilizumab (as applicable). Women must refrain from donating eggs during this same period Agreement by males to abstain from heterosexual intercourse or use a condom with female partners of childbearing potential or pregnant female partners during the treatment period and for at least 2 months after the last dose of glofitamab, and at least 4 months after the last dose of obinutuzumab, or tocilizumab (as applicable) to avoid exposing the embryo. Men must refrain from donating sperm during this same period
‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) with no identified cause other than menopause
∙ Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices, and copper intrauterine devices