A multi-center, open-label, phase 2 clinical study to evaluate the safety and efficacy of the investigational drug BGB-A317 in patients with T-cell or NK-cell lymphoma
- Conditions
- Relapsed or Refractory Mature T- and NK-cell NeoplasmsTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]MedDRA version: 20.0Level: HLGTClassification code 10025321Term: Lymphomas non-Hodgkin's T-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders
- Registration Number
- EUCTR2017-003700-44-IT
- Lead Sponsor
- BEIGENE USA, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 130
1. Histologically confirmed diagnosis of relapsed or refractory, mature Tcell and NK-cell neoplasms based on the WHO 2016 classification of tumors of hematopoietic and lymphoid tissue. Patients will be allocated to one of three cohorts based on their histologic diagnosis:
• Cohort 1: Extranodal NK/T-cell lymphoma (nasal or non-nasal type)
¿ Patients with aggressive NK leukemia are excluded
• Cohort 2: Other mature T-cell neoplasms, limited to the following histologies:
¿ Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)
¿ Angioimmunoblastic T-cell lymphoma (AITL)
¿ Anaplastic large cell lymphoma (ALCL)
• Cohort 3: Stage IB-IVB cutaneous T-cell lymphomas, limited to the following histologies (Appendix 15):
¿ Mycosis fungoides (MF)
¿ Sèzary syndrome (SS)
2. Male or female = 18 years of age at the time of informed consent (or acceptable age according to local regulations, whichever is older)
3. Previously received 1 or more appropriate systemic therapies (e.g., non-anthracycline based regimens, such as L-asparaginase-based therapy) for cohort 1 or combination chemotherapy (e.g. CHOP, EPOCH,or similar therapy) for cohort 2. Radiation therapy alone would not be acceptable as previous therapy.
• For patients with relapsed or refractory anaplastic large cell lymphoma, regardless of anaplastic lymphoma kinase (ALK) status, must have received prior therapy with brentuximab vedotin (applicable only to countries where brentuximab vedotin received marketing approval)
4. Disease progression during or after completion of most recent therapy or refractory disease. Refractory disease is defined as failure to achieve CR or PR to most recent therapy, and most recent therapy was an appropriate systemic therapy for mature T-cell or NK-cell lymphoma
5. For cohorts 1 and 2, patients must have lesions that are measurable by imaging, where measurable is defined as = 1 lesion that is > 1.5 cm for nodal lesions and > 1 cm for extranodal lesions. For cohort 3, patients are not required to have measurable disease by
imaging.
6. Availability of either unstained tissue (block or unstained slides) or stained slides, and pathology report for central confirmation of mature T-cell or NK-cell lymphoma. If stained slides or unstained tissue (block or unstained slides) are not available or are insufficient, a fresh tumor tissue sample is mandatory for central pathology. Central pathology confirmation is not required prior to enrollment.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see table 3 in protocol).
8. Has life expectancy = 6 months.
9. Patients must have forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), carbon monoxide diffusion capacity (DLCO) > 60% predicted value, and FEV1 and FVC > 50% predicted value; all PFTs must be obtained within 4 weeks prior to the first dose of tislelizumab
10. Adequate organ function defined as:
• Absolute neutrophil count (ANC) > 1000/mm3(without growth factor support within 7 days of ANC measurement)
• Platelet > 50000/mm3(without growth factor support or transfusion within 7 days of platelets measurement)
• Hemoglobin > 80 g/L (prior transfusion is acceptable)
• Creatinine clearance = 30 ml/min (as estimated by the CockcroftGault equation or as measured by nuclear medicine scan or 24-hour urine collection) (see Appendix 9 of protocol)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine am
1. Known central nervous system involvement by leukemia or lymphoma
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agent
3. Meets one of the following scenarios for hematopoietic stem cell transplantation and/or chimeric antigen receptor T cell (CAR-T) therapy:
• Is eligible for autologous or allogeneic stem cell transplantation, unless patient has refused transplantation
• Has undergone prior allogeneic hematopoietic stem cell transplantation or organ transplantation
• Has received autologous stem cell transplantation within 6 months prior to first dose of study drug
• Has received CAR-T therapy within 12 months prior to the first dose of study drug
4. Has received:
• Systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (or 5 half-lives, whichever is shorter) prior to study Day 1
• Recent treatment with another monoclonal antibody within 4 weeks prior to study Day 1
• Investigational treatment or device within 4 weeks (or 5 half-lives,whichever is shorter) prior to study Day 1
• For cohort 3 patients, phototherapy within 2 weeks or any topical therapy within 1 week prior to study Day 1
• Or has not recovered from AEs (ie, = Grade 1 or baseline level) due to prior therapy.
5. Concurrent or prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 or lower prostate cancer
6. Active autoimmune diseases or history of autoimmune diseases that may relapse (see Appendix 3) Note: Patients with the following diseases are not excluded and may proceed to further screening:
a. Type I diabetes under control
b. Hypothyroidism (provided it is managed with hormone replacementtherapy only)
c. Controlled celiac disease
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis,alopecia), except when such diseases significantly interfere with response assessment of patients in cohort 3
e. Any other disease that is not expected to recur in the absence ofexternal triggering factors
7. Has known history of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung diseases or evidence of dyspnea at rest or pulse oximetry of < 92% while breathing room air
8. Has any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before study drug administration. Note: Patients who are currently or have previously been
on any of the following steroid regimens are not excluded:
a. Adrenal replacement steroid (dose = 10 mg daily of prednisone or equivalent)
b. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption, except when given for treatment of MF or SS
c. 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
9. Has a known active TB (Bacillus Tuberculosis) infection
10. Known infection with HIV, human T-cell lymphotropic virus-1, -2, or 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
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