Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
A Phase I Study of Glofitamab With Alternating R-CHOP/R-DHAP in Previously Untreated Mantle Cell Lymphoma
4 other identifiers
interventional
16
0 countries
N/A
Brief Summary
This phase I trial tests the safety, side effects and best dose of glofitamab given with alternating cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)/ rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) for the treatment of mantle cell lymphoma. Glofitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. 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). Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone and dexamethasone are in a class of medications called corticosteroids. They are used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Chemotherapy drugs, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Giving glofitamab may be safe, tolerable and/or effective in treating patients with mantle cell lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2026
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2026
CompletedFirst Posted
Study publicly available on registry
March 3, 2026
CompletedStudy Start
First participant enrolled
August 20, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
Study Completion
Last participant's last visit for all outcomes
September 1, 2027
May 13, 2026
March 1, 2026
1 year
February 28, 2026
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events (AEs)
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 for all AEs other than cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH). CRS, ICANS, and HLH will be graded according to American Society for Transplantation and Cellular Therapy criteria.
Up to 5 years
Dose limiting toxicity (DLT)
DLT is defined as any grade 4 or higher CRS event, any grade CRS event that does not improve to \< grade 2 within 72 hours, any grade 3 or higher neurologic toxicity event including ICANS events, any grade 3 or higher non-hematologic toxicity, grade 3 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation that does not resolve to grade 2 or less within 14 days, grade 4 AST or ALT is a DLT regardless of duration, grade 4 thrombocytopenia lasting more than 7 days, grade 3 thrombocytopenia with hemorrhage, grade 3 thrombocytopenia lasting ≥ 28 days or grade 4 neutropenia lasting ≥ 14 days despite the use of growth factors.
From cycle 2, day 8 to cycle 5 day 1 (cycle length = 21 days)
Secondary Outcomes (5)
Overall response rate
From completion of induction therapy, up to 5 years
Complete response rate
Up to 5 years
Partial response rate
Up to 5 years
Failure free survival
From enrollment to stable disease at the end of induction therapy, progressive disease, or death from any cause, up to 5 years
Overall survival
From enrollment to death from any cause, up to 5 years
Other Outcomes (2)
Minimal residual disease negativity
After completion of induction therapy before initiation of maintenance therapy and every 6 months during maintenance therapy
Complete of at least 4 cycles of therapy (feasibility)
Up to 5 years
Study Arms (1)
Treatment (glofitamab with R-CHOP/R-DHAP)
EXPERIMENTALINDUCTION: CYCLES: 1, 3 and 5: Patients receive rituximab IV, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1, as well as prednisone PO on days 1-5. Starting with cycle 3, patients also receive glofitamab IV, over 2-8 hours, on day 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. CYCLES 2, 4 and 6: Patients receive rituximab IV, and cisplatin IV over 24 hours on day 1, as well as cytarabine IV on day 2 and dexamethasone PO on days 1-4. Patients also receive glofitamab IV, over 2-8 hours, on days 8 and 15 of cycle 2 and on day 8 of subsequent cycles. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive glofitamab IV on day 1 of each cycle. Cycles repeat every 21 days for a total of 24 months of treatment, in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo blood sample collection
Given IV
Undergo CT scan
Given IV
Given IV
Given PO
Given IV
Given IV
Undergo PET scan
Given PO
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed previously untreated mantle cell lymphoma which is stage II bulky, stage III, or stage IV and fit for intensive chemotherapy. TP53 mutated patients are eligible
- Patients must exhibit measurable disease by PET or CT imaging with at least one site of disease \> 1.5 cm in longest dimension or documented bone marrow involvement
- Age ≥ 18 years to ≤ 75 years. Because no dosing or adverse event data are currently available on the use of glofitamab in combination with R-CHOP/R-DHAP in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Absolute neutrophil count ≥ 1,000/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 2 × institutional upper limit of normal (ULN) unless total bilirubin elevation is attributable to Gilbert's syndrome or lymphomatous infiltration of the liver in whom total bilirubin must be \< 3 times ULN
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN
- Creatinine clearance ≥ 30 ml/min
- Left ventricular ejection fraction ≥ 45% by echocardiogram or Multiple-Gated Acquisition (MUGA) scan
- International Normalized Ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN in the absence of therapeutic anticoagulation
- Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN in the absence of a lupus anticoagulant
- Hemoglobin (Hgb) ≥ 8 g/dL
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- +7 more criteria
You may not qualify if:
- Patients who received prior treatment for MCL, including chemotherapy, bispecific antibody therapy, or other cytotoxic or cellular therapy including autologous hematopoietic stem cell transplant (autoHCT). Since this study aims to evaluate safety and efficacy in previously untreated patients by using this regimen as a first-line therapy, prior systemic therapy would potentially bias and affect endpoints and results
- Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients with lymphoma that shows active and uncontrolled CNS involvement; uncontrolled CNS involvement may require different systemic therapy in addition to CNS directed therapy, which would interfere with the study regimen and sequence of drug administration
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to glofitamab or other agents used in study
- Patients with active, uncontrolled infection defined as ongoing signs or symptoms of infection despite antimicrobial therapy or other infection-directed therapy
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous
- Pregnant women are excluded from this study because glofitamab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with glofitamab, breastfeeding should be discontinued if the mother is treated with glofitamab. These potential risks may also apply to other agents used in this study
- Patients with prior solid organ transplantation
- Prior treatment with systemic immunotherapeutic agents, including but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (mAbs) (e.g., anticytotoxic T lymphocyte associated protein 4, anti-PD-1, and anti-PD-L1) within 4 weeks or five half-lives of the drug, whichever is shorter
- Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of cycle 1
- Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of cycle 1
- Prior radiotherapy to the mediastinal/pericardial region. Radiotherapy to non-target lesion sites will be permitted
- Corticosteroid use \> 50 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control.
- Participants receiving corticosteroid treatment with ≤ 50 mg/day of prednisone or equivalent for reasons other than lymphoma symptom control (e.g., rheumatoid arthritis) must be documented to be on a stable dose of at least 4 weeks duration prior to the start of cycle 1.
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Naseem Esteghamat
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2026
First Posted
March 3, 2026
Study Start (Estimated)
August 20, 2026
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
September 1, 2027
Last Updated
May 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.