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

NCT04981899 | Unknown Phase 1

• 1 other identifier: r/r cHL NICE-40
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

Hodgkin Lymphoma

Keywords

Nivolumab; Ifosfamide; Carboplatin; Etoposide

Outcome Measures

Primary Outcomes (2)

• Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03

  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).

  12 months

• Overall Response Rate (ORR)

  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

  12 months

Secondary Outcomes (3)

• Duration of Response (DOR)

  24 months

• Overall Survival (OS)

  24 months

• Progression-Free Survival (PFS)

  24 months

Study Arms (1)

Main arm

EXPERIMENTAL

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; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

Interventions

Nivolumab DRUG

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.

Main arm

Ifosfamide DRUG

5000 mg / m2, 24-hour infusion on day 2 of the NICE-40.

Main arm

Carboplatin DRUG

Optimized to get AUC = 5 (max. 800 mg) on day 2 of the NICE-40.

Main arm

Etoposide DRUG

100 mg / m2 intravenously on 1-3 days of the NICE-40.

Main arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (3)

National Medicine Research Center of oncology named after N.N. Petrov

Saint Petersburg, Pesochny, 197758, Russia

RECRUITING

Irkutsk Regional Cancer Center

Irkutsk, 664044, Russia

RECRUITING

St. Petersburg State Pavlov Medical University

Saint Petersburg, 197022, Russia

RECRUITING

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Nivolumab; Ifosfamide; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Alexander Kulagin, MD,PhD

  RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University

  STUDY DIRECTOR

Central Study Contacts

Kirill Lepik, MD,PhD

CONTACT

+78123386265; lepikkv@gmail.com

Natalia Mikhailova, MD,PhD

CONTACT

bmt.lymphoma@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science RM Gorbacheva Institute

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 29, 2021
• Study Start: March 1, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2024
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

RU (3)