Tislelizumab, Gemcitabine and Cisplatin for R/R Hodgkin Lymphoma Followed by Tislelizumab Consolidation in Patients in Metabolic Complete Remission

NCT05502250 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: HO1642022-502225-17
• Study Type: interventional
• Target: 75
• Locations: 3 countries
• Sites: 15

Brief Summary

This trial investigates the efficacy and safety of the drug tislelizumab in combination with chemotherapy as a treatment for patients with R/R HL. Tislelizumab is given in combination with chemotherapy (gemcitabine and cisplatin) followed by consolidation with tislelizumab alone. The study primary question is whether this strategy works as well as the standard treatment with intensive chemotherapy and autologous stem cell transplant.

Conditions

Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) probability at 2 years after registration. PFS is defined as time from registration to progression or death from any cause, whichever comes first.

  Single-arm

  Approximately up to 48 months following first patient enrollment

Secondary Outcomes (8)

• Overall response rate (ORR: mCR and mPR rates) (as assessed by FDG-PET/CT) after 2 and 4 cycles of tislelizumab in combination with GP chemotherapy induction.

  Approximately up to 28 months following first patient enrollment

• Rate of CTCAE grade 3/4 toxicities of tislelizumab in combination with GP chemotherapy.

  Approximately up to 28 months following first patient enrollment

• Rate of CTCAE grade 2 to 4 immune related toxicities of tislelizumab in combination with GP chemotherapy.

  Approximately up to 36 months following first patient enrollment

• Rate of CTCAE grade 3/4 toxicities of tislelizumab consolidation treatment.

  Approximately up to 36 months following first patient enrollment

• Progression free survival (PFS) as time-to-event outcome.

  Approximately up to 36 months following first patient enrollment

Study Arms (1)

Single-arm

EXPERIMENTAL

4 cycles of gemcitabine and cisplatin (GP) + tislelizumab followed by 13 cycles of tislelizumab

Drug: gemcitabine, cisplatin and tislelizumab

Interventions

gemcitabine, cisplatin and tislelizumab DRUG

All patients will receive 2 cycles of gemcitabine and cisplatin (GP) + tislelizumab. Each cycle lasts 21 days. Treatment is given through an IV line on day 1 and 8. After 2 cycles a FDG-PET-CT scan will be performed. Patients who respond well will proceed with 2 additional cycles of GP + tislelizumab . Patients with insufficient response will stop with the study treatment and they will continue treatment according to local practice. After 4 cycles of GP + tislelizumab another FDG-PET-CT scan will be performed. If this scan shows that the disease is under control (metabolic complete remission) patients will proceed with 13 cycles of tislelizumab consolidation treatment (21 day cycles). Treatment is given on day 1 through an IV line.

Single-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:

• Histologically confirmed classical HL (according to the latest version of the WHO classification).
• Primary refractory to first line chemotherapy, or in first relapse after any polychemotherapy regimen (e.g. ABVD, baseline BEACOPP or escalated BEACOPP, or other induction regimens).
• In case of relapse, the relapse must be histologically confirmed. In case histologic biopsy is not possible, at least confirmation of the relapse by fine needle aspirate (FNA) or sequential imaging is required.
• Measurable disease, based on Lugano criteria 2014 \[40\]; i.e. CT scans showing at least 2 or more clearly demarcated lesions with a long axis ≥ 1.5 cm and a short axis diameter ≥ 1.0 cm, or 1 clearly demarcated lesion with a long axis ≥ 2.0 cm and a short axis diameter ≥ 1.0 cm. These lesions must be FDG-PET-positive.
• Age 18-70 years inclusive.
• WHO/ECOG Performance Status ≤ 1 (see appendix C).
• No major organ dysfunction, unless HL-related:
• Total bilirubin \< 1.5x ULN (unless due to lymphoma involvement of the liver or a known history of Gilbert's syndrome; in that case bilirubin may be elevated up to 3 x ULN).
• ALT/AST \< 3x ULN (unless due to lymphoma involvement of the liver; in that case ALT/AST may be elevated up to 5 x ULN).
• GFR \> 60 ml/min as estimated by the Cockcroft\&Gault formula.
• Adequate BM function defined as:
• Absolute neutrophil count ≥ 1.5x109/L, unless caused by diffuse bone marrow infiltration by the HL.
• Platelets ≥ 75 x109/L, unless caused by diffuse bone marrow infiltration by the HL.
• Hemoglobin must be ≥ 8 g/dL (5 mmol/L).
• Resolution of toxicities from first-line therapy.

You may not qualify if:

• Previous treatment with an PD-1 or PDL-1 blocking agent.
• Patients who have been using other investigational agents within at least 5 half lives or 4 weeks, whichever is longer, of the most recent agent used prior to start of protocol treatment.
• Patients who were treated with myelosuppressive chemotherapy or biological therapy within at least 5 half lives or 4 weeks, whichever is longer, before start of protocol treatment.
• Patients who were treated with steroids for more than 25 mg /day for at least 14 days before start of protocol treatment.
• Patients receiving radiation therapy within 2 weeks prior to start of protocol treatment. Emergency radiation therapy is allowed, as long as measurable disease (at non-irradiated sites) persists.
• Prior allogeneic stem cell transplantation or solid organ transplantation.
• Peripheral neuropathy \> grade 2.
• Active autoimmune diseases or history of autoimmune diseases that may relapse.
• Note: Patients with the following diseases are not excluded and may proceed to further screening:
• Controlled Type I diabetes.
• Hypothyroidism (provided it is managed with hormone replacement therapy only).
• Controlled celiac disease.
• Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia).
• Any other auto-immune disease that is not expected to recur due to the protocol treatment.
• Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before study treatment.

Sponsors & Collaborators

• Danish Lymphoma Group: collaborator
• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead

Study Sites (15)

BE-Bruxelles-STLUC

Brussels, Belgium

Location

DK-Aarhus N-AUH

Aarhus, Denmark

Location

DK-Copenhagen-RIGSHOSPITALET

Copenhagen, Denmark

Location

DK-Odense-OUH

Odense, Denmark

Location

NL-Amersfoort-MEANDERMC

Amersfoort, Netherlands

Location

NL-Amsterdam-AMC

Amsterdam, Netherlands

Location

NL-Arnhem-RIJNSTATE

Arnhem, Netherlands

Location

NL-Eindhoven-MAXIMAMC

Eindhoven, Netherlands

Location

NL-Goes-ADRZ

Goes, Netherlands

Location

NL-Groningen-UMCG

Groningen, Netherlands

Location

NL-Hoofddorp-SPAARNEGASTHUIS

Hoofddorp, Netherlands

Location

NL-Leeuwarden-MCL

Leeuwarden, Netherlands

Location

NL-Maastricht-MUMC

Maastricht, Netherlands

Location

NL-Rotterdam-ERASMUSMC

Rotterdam, Netherlands

Location

NL-Den Haag-HAGA

The Hague, Netherlands

Location

Related Links

• Website of HOVON - the Haemato Oncology Foundation for Adults in the Netherlands

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Gemcitabine; Cisplatin; tislelizumab

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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm = 4 cycles of gemcitabine and cisplatin (GP) + tislelizumab followed by 13 cycles of tislelizumab

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: August 16, 2022
• Study Start: July 14, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2031
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

BE (1); NL (11); DK (3)