Trial Title:
Tislelizumab, Gemcitabine and Cisplatin for R/R Hodgkin Lymphoma Followed by Tislelizumab Consolidation in Patients in Metabolic Complete Remission
NCT ID:
NCT05502250
Condition:
Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Hodgkin Disease
Gemcitabine
Tislelizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single arm = 4 cycles of gemcitabine and cisplatin (GP) + tislelizumab followed by 13
cycles of tislelizumab
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
gemcitabine, cisplatin and tislelizumab
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.
Arm group label:
Single-arm
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
BE-Bruxelles-STLUC
Address:
City:
Brussels
Country:
Belgium
Status:
Recruiting
Facility:
Name:
DK-Aarhus N-AUH
Address:
City:
Aarhus
Country:
Denmark
Status:
Recruiting
Facility:
Name:
DK-Copenhagen-RIGSHOSPITALET
Address:
City:
Copenhagen
Country:
Denmark
Status:
Recruiting
Facility:
Name:
DK-Odense-OUH
Address:
City:
Odense
Country:
Denmark
Status:
Recruiting
Facility:
Name:
NL-Amersfoort-MEANDERMC
Address:
City:
Amersfoort
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Amsterdam-AMC
Address:
City:
Amsterdam
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Arnhem-RIJNSTATE
Address:
City:
Arnhem
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Den Haag-HAGA
Address:
City:
Den Haag
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Eindhoven-MAXIMAMC
Address:
City:
Eindhoven
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Goes-ADRZ
Address:
City:
Goes
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Groningen-UMCG
Address:
City:
Groningen
Country:
Netherlands
Status:
Recruiting
Investigator:
Last name:
W Plattel
Email:
Principal Investigator
Facility:
Name:
NL-Hoofddorp-SPAARNEGASTHUIS
Address:
City:
Hoofddorp
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Leeuwarden-MCL
Address:
City:
Leeuwarden
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Maastricht-MUMC
Address:
City:
Maastricht
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
NL-Rotterdam-ERASMUSMC
Address:
City:
Rotterdam
Country:
Netherlands
Status:
Recruiting
Start date:
July 14, 2023
Completion date:
April 2030
Lead sponsor:
Agency:
Stichting Hemato-Oncologie voor Volwassenen Nederland
Agency class:
Other
Collaborator:
Agency:
Danish Lymphoma Group
Agency class:
Other
Source:
Stichting Hemato-Oncologie voor Volwassenen Nederland
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05502250
https://hovon.nl/en
