Multicenter Study of Safety and Efficacy Nivolumab at the Fixed Dose 40 mg (Nivo40) in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed PMBL
- Registration Number
- NCT06188676
- Lead Sponsor
- National Research Center for Hematology, Russia
- Brief Summary
This compares the effects of nivolumab at a fixed dose of 40 mg 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 body's immune system attack the cancer, and may interfere with the ability of...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
Inclusion Criteria
- Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria Age 18-70 years old Ejection fraction greater than 50% ECOG 0-2 status Signed informed consent No severe concurrent illness measurable disease (at least one lesion that can be accurately measured in at least two dimensions on a CT scan, at least >15 mm in largest diameter
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Exclusion Criteria
- Uncontrolled bacterial or fungal infection at the time of enrollment
- Requirement for vasopressor support at the time of enrollment
- Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 norms
- Karnofsky index <30%
- Pregnancy
- Somatic or psychiatric disorder making the patient unable to sign an informed consent
- Active or prior documented autoimmune disease requiring systemic treatment.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A Rituximab Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses A Etoposide Phosphate Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses B Prednisolone (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. B Filgrastim (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. A Cyclophosphamide Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses A Vincristine Sulfate Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses B Etoposide Phosphate (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. B Vincristine Sulfate (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. B Rituximab (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. B Nivolumab 40 mg in 4 ml Injection (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. B Pegfilgrastim (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. A Doxorubicin Hydrochloride Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses A Prednisolone Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses A Filgrastim Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses A Pegfilgrastim Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 ANC is \>= 500/uL 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses B Cyclophosphamide (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses. B Doxorubicin Hydrochloride (DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg IV over 30 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 5 years The primary analysis will be a one-sided Log-rank test stratified by choice of backbone and radiation therapy and whether the patient had a cycle of therapy prior to enrolling.
- Secondary Outcome Measures
Name Time Method Efficacy-related event-free survival Up to 5 years Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as progression, change in therapy due to a finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, and death.
Therapy-related event-free survival Up to 5 years Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as progression, change in therapy due to a finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, and death.
Overall survival Up to 5 years Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as only death.
Trial Locations
- Locations (1)
National Research Center for Hematology
🇷🇺Moscow, Russian Federation