Testing the Addition of a New Anti-Cancer Drug, Glofitamab to Usual Chemotherapy for Burkitt and Double Hit Lymphoma

Trial statusNot yet recruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

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 volunteers

Qualifiers

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

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood and/or cerebrospinal fluid collection

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Carboplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Cyclophosphamide

    Drug

    Given IV

  • Cytarabine

    Drug

    Given IV or IT

  • Doxorubicin

    Drug

    Given IV

  • Etoposide

    Drug

    Given IV

  • Glofitamab

    Biological/Vaccine

    Given IV

  • Ifosfamide

    Drug

    Given IV

  • Lumbar Puncture

    Procedure/Surgery

    Undergo lumbar puncture

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Methotrexate

    Drug

    Given IV or IT

  • Obinutuzumab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET scan

  • Prednisone

    Drug

    Given PO

  • Rituximab

    Biological/Vaccine

    Given IV

  • Rituximab and Hyaluronidase Human

    Biological/Vaccine

    Given SC

  • Survey Administration

    Other intervention

    Ancillary studies

  • Vincristine

    Drug

    Given IV

Treatment groups

271 Participants
are divided into 5 treatment groups
Group A: Cohort 1 arm 2 RCODOXM/RIVAC or DA-REPOCH and glofitamab)Experimental treatment 18 interventions
Group B: Cohort 1, arm 1 RCODOXM/RIVAC or DA-REPOCH)Experimental treatment 17 interventions
Group C: Cohort 2 arm 3 (DA-REPOCH)Experimental treatment 16 interventions
Group D: Cohort 2 arm 4 (DA-REPOCH and glofitamab)Experimental treatment 16 interventions
Group E: Cohort 3 (RICE and glofitamab)Experimental treatment 16 interventions

Trial outcomes

Primary outcomes

1

Progression free survival (PFS) (cohort 1) (phase II)

The median PFS will be summarized by sex with corresponding 95% confidence intervals.

Time frame
from randomization to the time of documented disease progression or death due to any cause
2

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.

Time frame
At 24 months
3

PFS (cohort 2) (phase II)

The median PFS will be summarized by sex with corresponding 95% confidence intervals.

Time frame
From randomization to the time of documented disease progression or death due to any cause, up to 5 years
4

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.

Time frame
At 24 months

Secondary outcomes

1

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.

Time frame
From randomization to the time of death due to any cause, up to 5 years
2

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.

Time frame
From randomization date until the earlier of non-protocol lymphoma therapy, disease progression or death from any cause, up to 5 years
3

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.

Time frame
Up to 5 years
4

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.

Time frame
Up to 5 years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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