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

Phase 1

• Conditions: Relapsed or Refractory Mature T- and NK-cell Neoplasms; MedDRA version: 20.0Level: HLGTClassification code 10025321Term: Lymphomas non-Hodgkin's T-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-003700-44-FR
• Lead Sponsor: BeiGene, Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-02-19
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Histologically confirmed diagnosis of relapsed or refractory, mature T-cell and NK-cell neoplasms based on the WHO 2016 classification of tumors of hematopoietic and lymphoid tissue. Patients will be allocated to one of two cohorts based on their histologic diagnosis:
• Cohort 1: Extranodal NK/T-cell lymphoma
• Cohort 2: Other mature T-cell neoplasms, limited to the following histologies:
? Peripheral T-cell lymphoma - NOS
? Angioimmunoblastic T-cell lymphoma
? Anaplastic large cell lymphoma
2. Male or female = 18 years of age at the time of informed consent
3. Previously received 1 or more appropriate systemic therapies (such as L-asparaginase-based therapy for cohort 1, and combination chemotherapy such as CHOP, EPOCH, or similar therapy for cohort 2). Radiation therapy alone would not be acceptable previous therapy
4. Disease progression 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. Measurable lesions defined as = 1 lesion that is > 1.5 cm for nodal lesions and > 1 cm for extranodal lesions
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 are not available, a fresh tumor tissue sample is mandatory for central pathology and other biomarker analysis. 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. Patient must have forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), carbon monoxide diffusion capacity (DLCO), FEV1 and FVC all > 50% predicted value; all PFTs must be obtained within 4 weeks prior to the first dose of BGB-A317.
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 Cockcroft-Gault 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 aminotransferase
(ALT)/serum glutamic pyruvic transaminase = 3.0 × upper limit of normal (ULN)
• Serum total bilirubin < 2.0 × ULN (unless documented Gilbert’s syndrome)
11. Female patients of childbearing potential must be willing to use a highly effective method of birth control/contraception for the duration of the study, and for at least 120 days after the last dose of BGB-A317, and have a negative serum pregnancy test within 7 days of the first dose of study drug. Please refer to Appendix 4 for a list of acceptable birth control/contraception methods and contraceptive guidelines.
12. Non-sterile males must be willing to use a highly effective method of birth control/contraception for the duration of the study and for at least 120 days after the last dose of BGB-A317
13. Ability to provide written infor

Exclusion Criteria

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. Is eligible for allogeneic stem cell transplantation, unless patient has refused transplantation, or has undergone prior allogeneic hematopoietic stem cell transplantation or organ transplantation. Has received autologous stem cell transplantation within 6 months or CAR-T therapy within 12 months
4. Has received chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or has not recovered from adverse events (ie, = Grade 1 or baseline level) due to prior therapy
5. 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 replacement therapy only)
c. Controlled celiac disease
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
e. Any other disease that is not expected to recur in the absence of external 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
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 or HTLV, 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 if hepatitis B virus (HBV) DNA is < 1000 IU/mL, and if they are willing to undergo monthly monitoring of HBV-DNA and treatment with anti-viral therapy starting before first dose of study drug;
• Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
11. Active fungal, bacterial, and/or viral infection requiring systemic therapy
12. Vaccination with a live vaccine within 35 days prior to the first dose of study drug
13. Clinically significant cardiovascular disease including the following:
• Myocardial infarction within 6 months before screening
Unstable angina within 3 months before screening
• New York Heart Association Classification III or IV congestive heart failure
(Appen

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified