Prolgolimab Monotherapy or in Combination With Bendamustine for r/r Classical Hodgkin Lymphoma

NCT05757466 | Unknown Phase 2

• 1 other identifier: 27/22-н
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Prolgolimab is an anti-PD-1 inhibitor that has previously been shown to be effective and safe for the treatment of patients with melanoma. Given the mechanism of action, it is expected to be effective in patients with classical Hodgkin lymphoma (cHL). The use of PD-1 inhibitors in 2nd line treatment, as part of PET-adapted monotherapy/combination therapy, has already demonstrated a favorable toxicity profile, as well as a high efficacy, which may lead to increased survival of patients with r/r cHL. It has been demonstrated that long-term disease remission can be achieved after PD-1 inhibitor therapy, even in a group of heavily pretreated patients with relapsed/refractory cHL. The use of prolgolimab as part of PET-adapted therapy strategy in this study may allow to achieve a prolonged remission in patients with cHL who are highly sensitive to immunotherapy while omitting the autologous stem cell transplantation.

Conditions

Hodgkin Lymphoma

Keywords

Hodgkin lymphoma; Prolgolimab; PD-1 inhibitors; Bendamustine; Immunotherapy; Relapsed/refractory; Autologous stem cell transplantation,

Outcome Measures

Primary Outcomes (1)

• Overall response rate during prolgolimab monotherapy

  Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by Lugano and LYRIC criteria

  12 months

Secondary Outcomes (6)

• Frequency of grade 3 or higher treatment-related adverse events during prolgolimab monotherapy

  12 months

• Frequency of grade 3 or higher treatment-related adverse events during combination therapy (prolgolimab+bendamustine)

  24 months

• Overall response rate during combination therapy (prolgolimab+bendamustine)

  24 months

• 1-year and 2-year overall survival

  24 months

• 1-year and 2-year progression-free survival

  24 months

Study Arms (1)

Main arm

EXPERIMENTAL

Patients receive 6 cycles of prolgolimab monotherapy with subsequent assessment of response by PET/CT using Lugano and LYRIC criteria. Patients with complete response continue prolgolimab therapy for up to 24 cycles. Patients are switched to combination therapy with prolgolimab and chemotherapy (bendamustine) if the complete response is not achieved after 6 cycles of therapy or in case of relapse during prolgolimab monotherapy. Patients without complete response after 6 cycles of prolgolimab monotherapy or with relapse during monotherapy will receive 3 cycles of combination therapy with prolgolimab and bendamustine every 28 days. Collection of hematopoietic stem cells is performed at any stage of combination therapy. Response evaluation after 3 cycles of combination therapy is performed by PET/CT using Lugano and LYRIC criteria. Autologous stem cell transplantation is conducted in patients who achieve complete or partial response.

Drug: Prolgolimab; Drug: Combination with prolgolimab and bendamustine

Interventions

Prolgolimab DRUG

Prolgolimab monotherapy 1 mg/kg IV every 2 weeks up to a maximum of 24 cycles

Main arm

Combination with prolgolimab and bendamustine DRUG

Prolgolimab 1 mg/kg IV D1,15; Bendamustine 90 mg/m2 IV D1,2, 28-day cycle, maximum of 3 cycles;

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:

• Patients with a histologically verified diagnosis of cHL, refractory or relapsed after the first line of therapy
• Age 18-70 y
• Ejection fraction not less than 50%
• No severe concurrent illness
• ECOG status
• Use of highly effective contraceptive methods from the moment of signing the informed consent form, throughout the study and within 6 months after receiving the last dose of the drug.

You may not qualify if:

• Severe organ failure: creatinine \> 2 norms; alanine aminotransferase, aspartate aminotransferase \> 5 norms; bilirubin\> 1.5 norms;
• Respiratory failure \> grade 1 at the time of enrollment
• Requirement for vasopressor support at the time of enrollment
• Uncontrolled bacterial or fungal infection at the time of enrollment
• Active or prior documented autoimmune disease requiring systemic treatment
• Pregnancy, breastfeeding, planning pregnancy or parenthood during the study period
• Hypersensitivity or allergy to study drugs
• Somatic or mental pathology that does not allow to perform research procedures, including the signing of informed consent
• Simultaneous use of drugs or medical devices studied in other clinical trials
• Use of PD-1 inhibitors or bendamustine in the 1st line of therapy

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead
• N.N. Petrov National Medical Research Center of Oncology: collaborator

Study Sites (2)

St. Petersburg State Pavlov Medical University

Saint Petersburg, 197022, Russia

RECRUITING

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

RECRUITING

MeSH Terms

Conditions

Hodgkin Disease; Recurrence

Interventions

Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kirill Lepik, MD, PhD

  St. Petersburg State Pavlov Medical University

  PRINCIPAL INVESTIGATOR

• Natalia Mikhailova, MD

  St. Petersburg State Pavlov Medical University

  STUDY CHAIR

Central Study Contacts

Kirill Lepik, MD, PhD

CONTACT

+78123386265; lepikkv@gmail.com

Liudmila Fedorova, MD

CONTACT

+78123386265; md.FedorovaL@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: February 17, 2023
• First Posted: March 7, 2023
• Study Start: April 19, 2023
• Primary Completion: March 10, 2024
• Study Completion: March 10, 2025
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

RU (2)