| Eligibility |
Inclusion Criteria:
- 1. Voluntary agreement to provide written informed consent;
- 2. Males and females who are =18 years old;
- 3. Patients must have an advanced hematologic malignancy including: Relapsed or
refractory lymphoma as defined by World Health Organization(WHO) criteria; Relapsed or
refractory AML /MDSas defined by World Health Organization (WHO) criteria;
- 4. Subjects must have documented CD70-positive .
- 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- 7. Expected survival time =3 months;
- 8.Have at least 1 evaluable lesion per Lugano 2014;
- 9. The function of major organs must meet the following criteria (Lymphoma:have not
received blood transfusion, EPO, G-CSF or other medical supportive treatment within 7
days before the first dose of study drug) :
- White blood cell count=25×109/L(for AML/MDS)
- Absolute neutrophil count (ANC) =1.5×109/L or =0.75×109 /L for patients with bone
marrow infiltration, Platelet =75×109 /L or =50×109 /L for patients with bone
marrow infiltration; Hemoglobin =8.0mmol/L or = 7.0mmol/L for patients with bone
marrow infiltration;
- International normalized ratio (INR) or prothrombin time (PT) =1.5×ULN; Activated
Partial Thromboplastin Time (APTT) =1.5×ULN;
- serum creatinine=1.5×ULN or Creatinine clearance rate =60 mL/min ;
- Total bilirubin =1.5×ULN or =3×ULN for patients with Gilbert's syndrome or liver
metastasis; Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)
=2.5×ULN or =5×ULN for patients with liver metastasis:
- 10. Women of child bearing potential and non-sterilized male patients who are sexually
active with a female partner of child bearing potential must agree to use an effective
method of contraception from screening until 6 months after the last dose of study
drug. Effective methods of contraception consist of prior sterilization, intrauterine
device, intrauterine hormone-releasing system, oral or injectable contraceptives, and
sexual abstinence.
- 11. Patients will be able to communicate well with the investigator, understand and
comply with the requirements of the study.
Exclusion Criteria:
- 1. Pregnant or lactating women;
- 2. Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia,
primary central nervous system malignancies or invasion of the central nervous system
(except for those who are asymptomatic or stable and do not require treatment =4 weeks
before the first dose of study drug);
- 3. Has not recovered from adverse reactions caused by previous anti-tumor treatments
to = grade 1 or baseline (refer to NCICTCAE5.0 ), except for alopecia, pigmentation
and other toxicity judged no safety risk by the investigator;
- 4. Previous exposure to CD70-targeted agents;
- 5. Patients with Allergic history or hypersensitivity reaction to any components of
BR108 injection;
- 6. Patients with active bacterial, viral, fungal, mycobacterium, parasite or other
infection (except fungal infection of nail bed) within 7 days prior to enrollment and
requiring intravenous infusion therapy (except neoplastic fever);
- 7. Patients with inherited or acquired hemorrhagic diseases or severe coagulation
abnormalities of clinical significance( Such as diffuse intravascular coagulation
(DIC) autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, sickle cell
anemia, etc);
- 8. HBsAg or HBcAb positive, and HBV DNA positive; HCVAb positive and HCV RNA positive;
HIV positive; syphilis infection requiring systematic treatment ;
- 9. Subjects who have received live or attenuated vaccine within 4 weeks before the
first administration or planned to receive live vaccine during the study period;
- 10. History of any other malignancies within 3 years (except for basal cell carcinoma
of the skin, squamous cell carcinoma of the skin, superficial bladder cancer,
localized prostate cancer, cervical carcinoma in situ, stage I ductal carcinoma in
situ of the breast, and malignancies that have been cured (CR) within 2 years prior to
initial administration and are currently considered stable by the investigator with
minimal risk of recurrence);
- 11. Patients with serious cardiovascular and cerebrovascular diseases or other serious
organic diseases, including but not limited to:
- History of stroke ?intracranial hemorrhage ?unstable angina pectoris? congestive
heart failure (NYHA III-IV)?myocardial infarction?severe arrhythmias (e.g.,
persistent ventricular tachycardia, ventricular fibrillation) or congenital long
QT syndrome within 6 months before enrollment.
- Left ventricular ejection fraction (LVEF) < 50% in echocardiography (ECHO) or
muti-gate detection scan (MUGA) .
- Corrected QT interval prolongation >470ms.
- Patients with interstitial lung disease, severe lung dysfunction, severe
pulmonary fibrosis, or pulmonary infection requiring systematic treatment.
- 12. Subjects who have autoimmune disorders and need to rely on immunosuppressive
therapy or receive systemic therapy with a dose of =20mg/day of prednisone or other
equivalent hormones within 2 weeks before enrollment;
- 13. Patients have received other clinical trials within 4 weeks before the first dose
of study drug;
- 14.Subjects who have major surgery or severe trauma within 4 weeks prior to initial
dosing or plan to take major surgery during the trial period;
- 15. Treatment with prior anti-cancer therapy (including chemotherapy, endocrine
therapy, targeted therapy, etc.) must have been terminated at last 28 days or 5
half-lives (whichever is shorter) before study enrolment,2 weeks for endocrine therapy
and Chinese medicine treatment with anti-tumor indications or local palliative
radiotherapy for bone metastasis and pain relief within 2 weeks.
- 16. Prior allogeneic hematopoietic stem cell or organ transplantation; recent
Autologous hematopoietic stem cell transplantation(less than 3 months prior first
dosing of study drug);
- 17. Patients with any mental or cognitive impairment that may restrict the
understanding and implementation of the informed consent;
- 18. Other serious, uncontrollable concomitant diseases that may affect protocol
compliance or interfere with outcomes, or other serious or uncontrollable medical
conditions that the investigator believes may put subjects at risk for participating
in the study
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