A Study of Safety and Efficacy of PET-adapted Treatment With Nivolumab at the Fixed Dose 40 mg, Ifosfamide, Carboplatin, Etoposide (NICE-40) in Patients With Relapsed/Refractory Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
Nivolumab is an anti-PD-1 antibody highly effective in patients with relapsed/refractory classical Hodgkin lymphoma. A PET-adapted regimen of Nivo combined with ICE as first salvage therapy was shown to induce high response rates and favorable progression-free survival as a bridge to autologous stem cell transplantation, allowing to omit salvage chemotherapy in a substantial proportion of r\r cHL patients. This study evaluates the safety and efficacy of PET-adapted treatment of nivolumab at the fixed dose of 40 mg in combination with ifosfamide, carboplatin, and etoposide (NICE-40) in patients with relapsed/refractory Hodgkin Lymphoma.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Main arm Patients will receive 6 cycles of nivolumab at the fixed dose of 40 mg, with subsequent assessment of response by PET-CT. Patients with CR will proceed to ASCT. Patients with <CR after nivolumab monotherapy will be treated with 2 cycles of a combination of nivolumab at the fixed dose 40 mg, ifosfamide, carboplatin and etoposide (NICE-40), with subsequent PET-CT assessment. |
Drug: Nivolumab
6 infusions of nivolumab at a fixed dose of 40 mg, 14 days apart, and infusion of nivolumab on day 0 of the NICE-40.
Drug: Ifosfamide
5000 mg / m2, 24-hour infusion on day 2 of the NICE-40.
Drug: Carboplatin
Optimized to get AUC = 5 (max. 800 mg) on day 2 of the NICE-40.
Drug: Etoposide
100 mg / m2 intravenously on 1-3 days of the NICE-40.
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Outcome Measures
Primary Outcome Measures
- Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03 [12 months]
Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).
- Overall Response Rate (ORR) [12 months]
Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by LYRIC and Lugano 2014 criteria
Secondary Outcome Measures
- Duration of Response (DOR) [24 months]
- Overall Survival (OS) [24 months]
- Progression-Free Survival (PFS) [24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis: Histologically confirmed Hodgkins lymphoma
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Relapsed or refractory disease after the first line of treatment
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Age 18-70 years old
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Ejection fraction greater than 50%
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ECOG 0-2 status
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Signed informed consent
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No severe concurrent illness
Exclusion Criteria:
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Uncontrolled bacterial or fungal infection at the time of enrollment
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Requirement for vasopressor support at the time of enrollment
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Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 norms
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Karnofsky index <30%
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Pregnancy
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Somatic or psychiatric disorder making the patient unable to sign an informed consent
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Active or prior documented autoimmune disease requiring systemic treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | National Medicine Research Center of oncology named after N.N. Petrov | Saint Petersburg | Pesochny | Russian Federation | 197758 |
2 | Irkutsk Regional Cancer Center | Irkutsk | Russian Federation | 664044 | |
3 | St. Petersburg State Pavlov Medical University | Saint Petersburg | Russian Federation | 197022 |
Sponsors and Collaborators
- St. Petersburg State Pavlov Medical University
Investigators
- Study Director: Alexander Kulagin, MD,PhD, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- r/r cHL NICE-40