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

Sponsor

St. Petersburg State Pavlov Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04981899

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

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
Hodgkin Lymphoma	Drug: Nivolumab Drug: Ifosfamide Drug: Carboplatin Drug: Etoposide	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter 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

Actual Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

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

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis: Histologically confirmed Hodgkins lymphoma
Relapsed or refractory disease after the first line of treatment
Age 18-70 years old
Ejection fraction greater than 50%
ECOG 0-2 status
Signed informed consent
No severe concurrent illness

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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