Acalabrutinib, Obinutuzumab, and Glofitamab for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

NCT06054776 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 22402NCI-2023-06838P30CA033572
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of unacceptable adverse events (AEs) (safety lead-in)

  Defined as AEs that is at least possibly related to study treatment and not related to underlying lymphoma. Toxicities will be graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Cytokine release syndrome (CRS) severity will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading Criteria. Observed toxicities will be summarized by type, severity, and attribution.

  During the first 2 cycles of treatment (cycle= 21 days)

• Complete response (CR) rate (phase 2)

  The proportion of response-evaluable participants that achieve a best response of CR after the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy. Will be estimated along with the 95% exact binomial confidence interval.

  Up to 4 years from start of treatment.

Secondary Outcomes (7)

• Minimal residual disease (MRD) negatively rate

  Up to 4 years from start of treatment

• Time to response

  From start of protocol treatment to the first achievement of partial response (PR) or CR, assessed up to 4 years from start of treatment

• Duration of response

  Defined as the time from the first achievement of PR or CR to time of progressive disease or death, whichever earlier, assessed up to 4 years from start of treatment

• Progression-free survival

  From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 4 years from start of treatment

• Overall survival

  From start of protocol treatment to time of death due to any cause, assessed up to 4 years from start of treatment

Study Arms (1)

Treatment (acalabrutinib, obinutuzumab, glofitamab)

EXPERIMENTAL

Patients recieve acalabrutinib PO BID of each cycle, obinutuzumab IV on days 1 and 7 of cycle 1 only, and glofitamab IV over 2-4 hours on days 8 and 15 of cycle 1 and day 1 of each subsequent cycle. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with MRD positive CR, PR, or SD after 12 cycles of protocol therapy may continue receiving single agent acalabrutinib per standard of care during the follow-up phase of the study. Patients also undergo a ECHO or MUGA during screening, as well as PET/CT or CT, and blood specimen collection throughout the trial. Patients may also undergo bone marrow biopsies throughout the trial.

Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: Glofitamab; Procedure: Multigated Acquisition Scan; Biological: Obinutuzumab; Procedure: Positron Emission Tomography

Interventions

Computed Tomography PROCEDURE

Undergo PET/CT or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Glofitamab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody RO7082859, RO 7082859, RO7082859

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsies

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (acalabrutinib, obinutuzumab, glofitamab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior treatment with a T-cell engaging bispecific antibody
• Prior therapeutic intervention with any of the following: therapeutic anti-cancer antibodies within 4 weeks (i.e. rituximab); radio- or toxin-immunoconjugates within 4 weeks; all other chemotherapy or radiation therapy within 2 weeks prior to day 1 of protocol therapy
• Prior exposure to a BTK inhibitor (including but not limited to ibrutinib, acalabrutinib, zanubrutinib, and pirobrutinib) for more than 180 cumulative days prior to enrollment. Patients with =\< 180 cumulative days on BTK inhibitor prior to enrollment are allowed, as long as they did not progress on treatment.
• Prior chimeric antigen receptor (CAR) T cell therapy within 6 months of day 1 of protocol therapy
• Prior allogeneic stem cell transplant
• Autologous hematopoietic stem cell transplant within 3 months of day 1 of protocol therapy
• Major surgical procedure (under general anesthesia) within 30 days of day 1 of protocol therapy.
• Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
• Systemic steroid therapy for any cause must be tapered down to =\< 20 mg/day prednisone or equivalent. Exceptions are:
• Use of brief ( =\< 7 days) course of high dose corticosteroids (100 mg/day prednisone or equivalent) prior to initiation of study therapy for control of lymphoma-related symptoms
• Inhaled or topical steroids
• Use of mineralocorticoids for management of orthostatic hypotension
• Use of physiologic doses of corticosteroids for management of adrenal insufficiency
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 2 weeks or five half-lives (whichever is shorter) prior to first dose of study treatment
• Live virus vaccines within 30 days prior to day 1 of protocol therapy or planned administration of live virus vaccines during glofitamab therapy

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinib; Specimen Handling; Biopsy; glofitamab; obinutuzumab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• John H Baird

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: September 26, 2023
• Study Start: December 2, 2024
• Primary Completion (Estimated): October 16, 2026
• Study Completion (Estimated): October 16, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

US (1)