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Tislelizumab, Gemcitabine and Cisplatin for R/R Hodgkin Lymphoma Followed by Tislelizumab Consolidation in Patients in Metabolic Complete Remission (HOVON164HL)

Primary Purpose

Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
gemcitabine, cisplatin and tislelizumab
Sponsored by
Stichting Hemato-Oncologie voor Volwassenen Nederland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Negative pregnancy test at study entry.
  • Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through at least 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
  • Male patient, even if surgically sterilized, (i.e., status post vasectomy) agrees to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
  • Written informed consent.
  • Patient is capable of giving informed consent.

Exclusion Criteria:

  • 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.

Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:

  • Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent).
  • Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption.
  • Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen).

    • History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
    • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML).
    • Patients who have a history of another primary malignancy less than 2 years before study inclusion or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix.
    • Patients with any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose.
    • Patients with active HIV (unless viral load undetectable and CD4 counts within the normal range under antiretroviral therapy), active HBV (e.g. HBV DNA PCR positive or HBV surface antigen-positivity), or active HCV (e.g. HCV RNA detected). Patients with inactive HBV are eligible, but antiviral prophylaxis is obligatory.
    • Patients who have any severe and/or uncontrolled cardiovascular condition that could affect their participation in the study such as:
  • Known history of symptomatic congestive heart failure (NYHA III, IV), myocardial infarction ≤ 6 months prior to first study drug.
  • Evidence of current serious uncontrolled cardiac arrhythmia, angina pectoris, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • History of cerebrovascular accident ≤ 6 months before study treatment.

    • Patient who was administered a live vaccine ≤ 4 weeks before study treatment.
    • A history of severe hypersensitivity reactions to chimeric or humanized antibodies or platinum-based compounds.
    • Breast-feeding female patients.
    • Current participation in another clinical trial with medicinal products.
    • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Sites / Locations

  • BE-Bruxelles-STLUC
  • DK-Aarhus N-AUH
  • DK-Copenhagen-RIGSHOSPITALET
  • DK-Odense-OUH
  • NL-Amersfoort-MEANDERMC
  • NL-Amsterdam-AMCRecruiting
  • NL-Arnhem-RIJNSTATE
  • NL-Den Haag-HAGA
  • NL-Eindhoven-MAXIMAMC
  • NL-Goes-ADRZ
  • NL-Groningen-UMCG
  • NL-Hoofddorp-SPAARNEGASTHUIS
  • NL-Leeuwarden-MCL
  • NL-Maastricht-MUMC
  • NL-Rotterdam-ERASMUSMC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single-arm

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Single-arm
Rate of CTCAE grade 3/4 toxicities of tislelizumab in combination with GP chemotherapy.
Single-arm
Rate of CTCAE grade 2 to 4 immune related toxicities of tislelizumab in combination with GP chemotherapy.
Single-arm
Rate of CTCAE grade 3/4 toxicities of tislelizumab consolidation treatment.
Single-arm
Progression free survival (PFS) as time-to-event outcome.
Single-arm
Event free survival (EFS) defined as time from registration to start new HL treatment, progression or death from any cause, whichever comes first.
Single-arm
Disease free survival (DFS) defined as time from start of consolidation therapy to relapse or death from any cause, whichever comes first.
Single-arm
Overall survival (OS) defined as time from registration to death from any cause.
Single-arm

Full Information

First Posted
May 25, 2022
Last Updated
July 14, 2023
Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborators
Danish Lymphoma Group
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1. Study Identification

Unique Protocol Identification Number
NCT05502250
Brief Title
Tislelizumab, Gemcitabine and Cisplatin for R/R Hodgkin Lymphoma Followed by Tislelizumab Consolidation in Patients in Metabolic Complete Remission
Acronym
HOVON164HL
Official Title
Tislelizumab Plus Gemcitabine and Cisplatin for Relapsed or Refractory Hodgkin Lymphoma Followed by Tislelizumab Consolidation in Patients in Metabolic Complete Remission (TIGERR-HL). An Open Label Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 14, 2023 (Actual)
Primary Completion Date
April 2027 (Anticipated)
Study Completion Date
April 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborators
Danish Lymphoma Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single arm = 4 cycles of gemcitabine and cisplatin (GP) + tislelizumab followed by 13 cycles of tislelizumab
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single-arm
Arm Type
Experimental
Arm Description
4 cycles of gemcitabine and cisplatin (GP) + tislelizumab followed by 13 cycles of tislelizumab
Intervention Type
Drug
Intervention Name(s)
gemcitabine, cisplatin and tislelizumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
Single-arm
Time Frame
Approximately up to 48 months following first patient enrollment
Secondary Outcome Measure Information:
Title
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.
Description
Single-arm
Time Frame
Approximately up to 28 months following first patient enrollment
Title
Rate of CTCAE grade 3/4 toxicities of tislelizumab in combination with GP chemotherapy.
Description
Single-arm
Time Frame
Approximately up to 28 months following first patient enrollment
Title
Rate of CTCAE grade 2 to 4 immune related toxicities of tislelizumab in combination with GP chemotherapy.
Description
Single-arm
Time Frame
Approximately up to 36 months following first patient enrollment
Title
Rate of CTCAE grade 3/4 toxicities of tislelizumab consolidation treatment.
Description
Single-arm
Time Frame
Approximately up to 36 months following first patient enrollment
Title
Progression free survival (PFS) as time-to-event outcome.
Description
Single-arm
Time Frame
Approximately up to 36 months following first patient enrollment
Title
Event free survival (EFS) defined as time from registration to start new HL treatment, progression or death from any cause, whichever comes first.
Description
Single-arm
Time Frame
Approximately up to 84 months following first patient enrollment
Title
Disease free survival (DFS) defined as time from start of consolidation therapy to relapse or death from any cause, whichever comes first.
Description
Single-arm
Time Frame
Approximately up to 84 months following first patient enrollment
Title
Overall survival (OS) defined as time from registration to death from any cause.
Description
Single-arm
Time Frame
Approximately up to 84 months following first patient enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Able to adhere to the study visit schedule and other protocol requirements. Negative pregnancy test at study entry. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through at least 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. Male patient, even if surgically sterilized, (i.e., status post vasectomy) agrees to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. Written informed consent. Patient is capable of giving informed consent. Exclusion Criteria: 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. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded: Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent). Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen). History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML). Patients who have a history of another primary malignancy less than 2 years before study inclusion or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix. Patients with any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose. Patients with active HIV (unless viral load undetectable and CD4 counts within the normal range under antiretroviral therapy), active HBV (e.g. HBV DNA PCR positive or HBV surface antigen-positivity), or active HCV (e.g. HCV RNA detected). Patients with inactive HBV are eligible, but antiviral prophylaxis is obligatory. Patients who have any severe and/or uncontrolled cardiovascular condition that could affect their participation in the study such as: Known history of symptomatic congestive heart failure (NYHA III, IV), myocardial infarction ≤ 6 months prior to first study drug. Evidence of current serious uncontrolled cardiac arrhythmia, angina pectoris, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. History of cerebrovascular accident ≤ 6 months before study treatment. Patient who was administered a live vaccine ≤ 4 weeks before study treatment. A history of severe hypersensitivity reactions to chimeric or humanized antibodies or platinum-based compounds. Breast-feeding female patients. Current participation in another clinical trial with medicinal products. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
S. Tonino
Phone
+31 (0)10 7041560
Email
s.h.tonino@amsterdamumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
W Plattel
Phone
+31 (0)10 7041560
Email
w.j.plattel@umcg.nl
Facility Information:
Facility Name
BE-Bruxelles-STLUC
City
Brussels
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Name
DK-Aarhus N-AUH
City
Aarhus
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Name
DK-Copenhagen-RIGSHOSPITALET
City
Copenhagen
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Name
DK-Odense-OUH
City
Odense
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Name
NL-Amersfoort-MEANDERMC
City
Amersfoort
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Amsterdam-AMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Arnhem-RIJNSTATE
City
Arnhem
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Den Haag-HAGA
City
Den Haag
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Eindhoven-MAXIMAMC
City
Eindhoven
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Goes-ADRZ
City
Goes
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Groningen-UMCG
City
Groningen
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
W Plattel
Facility Name
NL-Hoofddorp-SPAARNEGASTHUIS
City
Hoofddorp
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Leeuwarden-MCL
City
Leeuwarden
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Maastricht-MUMC
City
Maastricht
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
NL-Rotterdam-ERASMUSMC
City
Rotterdam
Country
Netherlands
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
https://hovon.nl/en
Description
Website of HOVON - the Haemato Oncology Foundation for Adults in the Netherlands

Learn more about this trial

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

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