About this trial
This phase II/III trial tests adding glofitamab to standard of care chemoimmunotherapy in patients with Burkitt and high grade (double hit) B- cell lymphomas that are newly diagnosed, that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Glofitamab 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. Obinutuzumab and rituximab are also monoclonal antibodies. They bind 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. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. 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. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Methotrexate is in a class of medications called antimetabolites. It is also a type of antifolate. Methotrexate stops cells from using folic acid to make DNA and may kill cancer cells. Chemotherapy drugs, such as cytarabine and ifosfamide, 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. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Giving glofitamab with standard of care chemotherapy may work well for the treatment of newly diagnosed, relapsed or refractory Burkitt and high grade (double hit) B- cell lymphomas.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Stage III or IV disease
Elevated lactate dehydrogenase (LDH) greater than institutional upper limit of normal (ULN)
Tumor mass ≥ 7 cm
BL COHORT 1: No prior treatment except for pre-phase chemotherapy, pre-phase corticosteroids, or one cycle of chemotherapy as described below.
Disqualifiers
None
Trial design
Parallel
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood and/or cerebrospinal fluid collection
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Carboplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT scan
Cyclophosphamide
DrugGiven IV
Cytarabine
DrugGiven IV or IT
Doxorubicin
DrugGiven IV
Etoposide
DrugGiven IV
Glofitamab
Biological/VaccineGiven IV
Ifosfamide
DrugGiven IV
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Methotrexate
DrugGiven IV or IT
Obinutuzumab
Biological/VaccineGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET scan
Prednisone
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Rituximab and Hyaluronidase Human
Biological/VaccineGiven SC
Survey Administration
Other interventionAncillary studies
Vincristine
DrugGiven IV
Treatment groups
Trial outcomes
Primary outcomes
Progression free survival (PFS) (cohort 1) (phase II)
The median PFS will be summarized by sex with corresponding 95% confidence intervals.
PFS (cohort 1) (phase III)
PFS defined as from randomization to the time of documented disease progression or death due to any cause. Will be as estimated using the methods of Kaplan and Meier. The median PFS and the 24-month PFS rates will be summarized by sex with corresponding 95% confidence intervals.
PFS (cohort 2) (phase II)
The median PFS will be summarized by sex with corresponding 95% confidence intervals.
PFS (cohort 2) (phase III)
PFS defined as from randomization to the time of documented disease progression or death due to any cause. Will be as estimated using the methods of Kaplan and Meier. The median PFS and the 24-month PFS rates will be summarized by sex with corresponding 95% confidence intervals.
Secondary outcomes
Overall survival (OS)
Will be evaluated between the treatment arms for each of the cohorts. Kaplan Meier methods will be used to estimate key aspects of the OS distributions for each of the treatment arms, and logrank tests will be used to compare these distributions between arms.
Event free survival (EFS)
Will be evaluated between the treatment arms for each of the cohorts. Kaplan Meier methods will be used to estimate key aspects of the EFS distributions for each of the treatment arms, and logrank tests will be used to compare these distributions between arms.
Overall response rate (ORR)
Defined as the number of patients achieving complete or partial response according to either the computed tomography(CT)-based or positron emission tomography (PET)-CT-based Lugano criteria, divided by the number of evaluable patients. will be estimated by treatment arm, and a 95% binomial confidence interval for the estimated ORR will be provided. Will be evaluated between the treatment arms for each of the cohorts.
Complete response rate
Defined as the number of patients achieving complete response according to either the CT-based or PET-CT-based Lugano criteria, divided by the number of evaluable patients. The CR rate will be estimated by treatment arm, and a 95% binomial confidence interval for the estimated CR rate will be provided.
Locations
Sponsors and contacts
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