Ignite Creation Date:
2024-05-06 @ 3:46 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04759586
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2021-02-17
Brief Title:
Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase 3 Trial of Nivolumab NSC 748726 in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-immunotherapy alone in treating patients with newly diagnosed primary mediastinal B-cell lymphoma PMBCL Immunotherapy with monoclonal antibodies such as nivolumab may help the bodys immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab Chemotherapy drugs 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 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 Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL
Detailed Description:
PRIMARY OBJECTIVE
I To determine if nivolumab chemo-immunotherapy results in a superior long term progression-free survival PFS events defined as disease progression confirmed by central review or death when compared with chemo-immunotherapy alone in patients with newly diagnosed primary mediastinal B-cell lymphoma
SECONDARY OBJECTIVES
I To compare the rates of efficacy-related event-free survival EFS eEFS events defined as progression change in therapy due to finding that led to concern about efficacy biopsy disease after 6 cycles of therapy or death between chemo-immunotherapy alone and chemo-immunotherapy nivolumab in patients with newly diagnosed PMBCL
II To compare the rates of therapy-related EFS tEFS events defined as relapseprogression change in therapy for any reason biopsy disease after 6 cycles of therapy secondary malignancy SMN or death between chemo-immunotherapy alone and chemo-immunotherapy nivolumab in patients with newly diagnosed PMBCL
III To compare the rates of overall survival OS between chemo-immunotherapy alone and chemo-immunotherapy nivolumab in patients with newly diagnosed PMBCL
IV To establish the rate of a positive positron emission tomography PET-computed tomography CT defined as Deauville score 4 or 5 at the completion of 6 cycles of nivolumab rituximab R- cyclophosphamide doxorubicin vincristine and prednisone CHOPdose-adjusted DA-etoposide prednisone vincristine cyclophosphamide and doxorubicin EPOCH-R and R-CHOPDA-EPOCH-R in patients with newly diagnosed PMBCL and evaluate the prognostic significance of such a finding
EXPLORATORY OBJECTIVES
I To bank radiology images for further studies II To bank specimens for future correlative studies III Characterize the immune profile of patients treated with nivolumab chemo-immunotherapy to identify markers predictive of response
IV Define the rate of complete response at the completion of initial planned therapy
OUTLINE Patients are randomly assigned to backbone therapy or backbone therapy nivolumab within each of 6 strata The strata are determined by physicians choice of backbone DA-EPOCH-R versus vs R-CHOP vs R-CHOP RT and whether or not the patient had 1 prior cycle of therapy
ARM A DA-EPOCH-R Patients receive prednisone or prednisolone orally PO once daily QD on days 1-5 and rituximab intravenously IV or rituximab and hyaluronidase human subcutaneously SC over 5 minutes on day 1 or 5 Patients also receive etoposide phosphate doxorubicin hydrochloride and vincristine sulfate IV over 96 hours on days 1-4 and cyclophosphamide IV over 30-60 minutes on day 5 Beginning 24-72 hours after completing cyclophosphamide patients receive filgrastim or pegylated filgrastim SC daily until absolute neutrophil count ANC is 500uL after the expected nadir Treatment repeats every 21 days for up to 6 cycles 5 if the patient had 1 prior cycle of treatment in the absence of disease progression or unacceptable toxicity Patients undergo echocardiography ECHO during screening and as clinically indicated and alumbar puncture LP for cerebral spinal fluid CSF collection optionally during screening Patients also undergo computed tomography CT or positron emission tomography PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM B DA-EPOCH-R NIVOLUMAB Patients receive treatment as in Arm A Patients also receive nivolumab IV over 30 minutes on day 1 Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM C R-CHOP Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5 Patients also receive cyclophosphamide IV over 30-60 minutes doxorubicin hydrochloride IV over 1-15 minutes or up to 60 minutes and vincristine sulfate IV over 1 or up to 60 minutes on day 1 Treatment repeats every 21 days for up to 6 cycles 5 if the patient had 1 prior cycle of treatment in the absence of disease progression or unacceptable toxicity Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM D R-CHOP NIVOLUMAB Patients receive treatment as in Arm C Patients also receive nivolumab IV over 30 minutes on day 1 Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM E R-CHOP RADIOTHERAPY Patients receive treatment as in Arm C Within 6-8 weeks after completion of chemotherapy patients undergo radiation therapy over 25 fractions Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM F R-CHOP RADIOTHERAPY NIVOLUMAB Patients receive treatment as in Arm D Within 6-8 weeks after completion of chemotherapy patients undergo radiation therapy over 25 fractions Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
After completion of study treatment patients are followed up every 3 months for year 1 every 6 months for years 2-3 and annually thereafter
I To determine if nivolumab chemo-immunotherapy results in a superior long term progression-free survival PFS events defined as disease progression confirmed by central review or death when compared with chemo-immunotherapy alone in patients with newly diagnosed primary mediastinal B-cell lymphoma
SECONDARY OBJECTIVES
I To compare the rates of efficacy-related event-free survival EFS eEFS events defined as progression change in therapy due to finding that led to concern about efficacy biopsy disease after 6 cycles of therapy or death between chemo-immunotherapy alone and chemo-immunotherapy nivolumab in patients with newly diagnosed PMBCL
II To compare the rates of therapy-related EFS tEFS events defined as relapseprogression change in therapy for any reason biopsy disease after 6 cycles of therapy secondary malignancy SMN or death between chemo-immunotherapy alone and chemo-immunotherapy nivolumab in patients with newly diagnosed PMBCL
III To compare the rates of overall survival OS between chemo-immunotherapy alone and chemo-immunotherapy nivolumab in patients with newly diagnosed PMBCL
IV To establish the rate of a positive positron emission tomography PET-computed tomography CT defined as Deauville score 4 or 5 at the completion of 6 cycles of nivolumab rituximab R- cyclophosphamide doxorubicin vincristine and prednisone CHOPdose-adjusted DA-etoposide prednisone vincristine cyclophosphamide and doxorubicin EPOCH-R and R-CHOPDA-EPOCH-R in patients with newly diagnosed PMBCL and evaluate the prognostic significance of such a finding
EXPLORATORY OBJECTIVES
I To bank radiology images for further studies II To bank specimens for future correlative studies III Characterize the immune profile of patients treated with nivolumab chemo-immunotherapy to identify markers predictive of response
IV Define the rate of complete response at the completion of initial planned therapy
OUTLINE Patients are randomly assigned to backbone therapy or backbone therapy nivolumab within each of 6 strata The strata are determined by physicians choice of backbone DA-EPOCH-R versus vs R-CHOP vs R-CHOP RT and whether or not the patient had 1 prior cycle of therapy
ARM A DA-EPOCH-R Patients receive prednisone or prednisolone orally PO once daily QD on days 1-5 and rituximab intravenously IV or rituximab and hyaluronidase human subcutaneously SC over 5 minutes on day 1 or 5 Patients also receive etoposide phosphate doxorubicin hydrochloride and vincristine sulfate IV over 96 hours on days 1-4 and cyclophosphamide IV over 30-60 minutes on day 5 Beginning 24-72 hours after completing cyclophosphamide patients receive filgrastim or pegylated filgrastim SC daily until absolute neutrophil count ANC is 500uL after the expected nadir Treatment repeats every 21 days for up to 6 cycles 5 if the patient had 1 prior cycle of treatment in the absence of disease progression or unacceptable toxicity Patients undergo echocardiography ECHO during screening and as clinically indicated and alumbar puncture LP for cerebral spinal fluid CSF collection optionally during screening Patients also undergo computed tomography CT or positron emission tomography PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM B DA-EPOCH-R NIVOLUMAB Patients receive treatment as in Arm A Patients also receive nivolumab IV over 30 minutes on day 1 Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM C R-CHOP Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5 Patients also receive cyclophosphamide IV over 30-60 minutes doxorubicin hydrochloride IV over 1-15 minutes or up to 60 minutes and vincristine sulfate IV over 1 or up to 60 minutes on day 1 Treatment repeats every 21 days for up to 6 cycles 5 if the patient had 1 prior cycle of treatment in the absence of disease progression or unacceptable toxicity Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM D R-CHOP NIVOLUMAB Patients receive treatment as in Arm C Patients also receive nivolumab IV over 30 minutes on day 1 Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM E R-CHOP RADIOTHERAPY Patients receive treatment as in Arm C Within 6-8 weeks after completion of chemotherapy patients undergo radiation therapy over 25 fractions Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
ARM F R-CHOP RADIOTHERAPY NIVOLUMAB Patients receive treatment as in Arm D Within 6-8 weeks after completion of chemotherapy patients undergo radiation therapy over 25 fractions Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening Patients also undergo CT or PETCT throughout the trial Additionally patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study Patients undergo blood sample collection on study
After completion of study treatment patients are followed up every 3 months for year 1 every 6 months for years 2-3 and annually thereafter
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA180886 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180886 |
| NCI-2021-01071 | REGISTRY | None | None |
| ANHL1931 | OTHER | None | None |
| ANHL1931 | OTHER | None | None |