Study of Tislelizumab in Patients with Relapsed or Refractory Hodgkin Lymphoma
- Conditions
- Refractory/relapse Hodgkin LymphomaMedDRA version: 20.0Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002105-22-ES
- Lead Sponsor
- BeiGene Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Male or female = 18 years
2. Histologically confirmed diagnosis of relapsed or refractory cHL
3. Relapsed cHL (disease progression after PR or CR to the most recent therapy).
Patients will be allocated to one of two cohorts based on the following criteria:
• Cohort 1: Relapsed or refractory to prior autologous HSCT
- Has failed to achieve a response or has had disease progression after autologous
HSCT
- Is not a candidate for additional autologous or allogeneic HSCT
• Cohort 2: Relapsed or refractory to salvage chemotherapy, and has not received prior
autologous or allogeneic HSCT
- Has received at least 1 prior systemic regimen for cHL
- Is not a candidate for autologous or allogeneic HSCT
4. Measurable disease defined as = 1 FDG-avid nodal lesion that is > 1.5 cm in the longest diameter, or = 1 FDG-avid extra-nodal lesion (eg, hepatic nodules) that is > 1 cm in the longest diameter
5. Able to provide fresh or archival tumor tissues (formalin-fixed paraffin-embedded [FFPE] blocks or approximately 15 freshly cut, unstained FFPE slides) from an evaluable core or excisional biopsy with an associated pathological report
6. ECOG performance status of 0 or 1
7. Life expectancy = 12 weeks
8. Adequate organ function, as indicated by the following laboratory values:
a. Absolute neutrophil count (ANC) = 1.0 x 109/L, independent of growth factor support
within 7 days of first dose
b. Platelet = 75 x 109/L, independent of transfusion, growth factor support or or
thrombopoietin receptor agonist within 7 days of first dose
c. Hemoglobin (Hgb) = 8 g/dL or = 5 mmol/L
d. Creatinine clearance > 30 mL/min
e. AST (SGOT) and ALT (SGPT) = 2.5 x the ULN or = 5 x ULN if liver lymphoma involvement is present
f. Serum total bilirubin = 1.5 x ULN (total bilirubin level < 4 x ULN for patients with
Gilbert syndrome)
9. No evidence of dyspnea at rest and a pulse oximetry of > 92% while breathing room air
of dyspnea at rest and a pulse oximetry of > 92% while breathing room air
10. DLCO (adjusted for alveolar volume) > 60% of predicted value; FEV1 and FVC,
FEV1/ FVC all > 50% predicted value
11. Female patients of childbearing potential must be willing to use a highly effective method
of contraception for the duration of the study and for = 120 days after the last dose of
tislelizumab, and have a negative urine or serum pregnancy test within 7 days before the
first dose of study drug.
12. Males are eligible to enter and participate in the study if they have been vasectomized or
if they agree to use barrier contraception with other highly effective methods during the study treatment period and for = 120 days after the last dose of
tislelizumab
13. Ability to provide written informed consent and can understand and comply with the
requirements of the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
1. Nodular lymphocyte-predominant Hodgkin lymphoma or gray zone lymphoma
2. Prior allogeneic hematopoietic stem cell transplantation
3. History of severe hypersensitivity reaction to monoclonal antibodies
4. New York Heart Association (NYHA) class III or IV heart failure, unstable angina,
severe uncontrolled ventricular arrhythmia, electrocardiographic evidence of acute
ischemia, or myocardial infarction within 6 months of first day of screening
5. Prior malignancy within the past 3 years except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or other site for which in situ carcinoma has metastatic potential
6. Prior therapy targeting PD-1, PD-L1, PD-L2, or CTLA-4 pathways
7. Has received:
- Systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to Cycle 1 Day 1
- Recent treatment with another monoclonal antibody within 4 weeks prior to Cycle 1 Day 1
- Investigational treatment or device within 4 weeks (or 5 half-lives, whichever is shorter) prior to Cycle 1 Day 1 and may qualify for the study if all other criteria are met)
8. Active autoimmune disease or history of autoimmune disease that may relapse
- Patients with the following are not excluded and may proceed to further screening:
Vitiligo, eczema, type I diabetes mellitus, and endocrine deficiencies including thyroiditis managed with replacement hormone and/or physiologic corticosteroids
- Patients with the following should be evaluated for the presence of target organ involvement and the potential need for systemic treatment, but should otherwise be eligible: Rheumatoid arthritis and/or other arthropathies, Sjögren’s syndrome, or
psoriasis controlled with topical medication, and patients with positive serology such
as positive antinuclear antibody or anti-thyroid antibody
9. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of tislelizumab
? Adrenal replacement doses of = 10 mg daily prednisone equivalent in the absence of
active autoimmune disease
? Topical, ocular, intra-articular, intranasal, and inhalational corticosteroid (with
minimal systemic absorption)
? A brief course of corticosteroid for prophylaxis (eg, contrast dye allergy) or for
treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction
caused by contact allergen)
10. History of interstitial lung disease or noninfectious pneumonitis or has evidence of
interstitial lung disease or noninfectious pneumonitis
11. Serious acute or chronic infection requiring systemic therapy
12. Known central nervous system (CNS) lymphoma
13. Underlying medical conditions that, in the investigator’s opinion, will render the
administration of study drug hazardous or obscure the interpretation of toxicity or AEs
14. Known history of infection with HIV, human T-cell lymphotropic virus-1, or human
T-cell lymphotropic virus-2
15. Serologic status reflecting active hepatitis B or C infection as follows:
? Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible only if hepatitis B virus (HBV) DNA is undetectable by an assay with sensitivity = 20 IU/mL. If so, patients may either undergo regularly scheduled monitoring of
HBV DNA or less frequent monitoring of HBV DNA while o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method