SG2501 Safety Study in Subjects with Relapsed or Refractory Hematological Malignancies and Lymphoma.

Inclusion Criteria

• •Patients must meet all the following criteria to be eligible for participation in this study:
• •1. Male or female ≥ 18 years.
• •2. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedurs.
• •1. Phase Ia,dose escalation:
• •• Patients with histologically or cytologically confirmed relapsed or refractory hematological malignancies and lymphoma based on WHO(2016) diagnosis who are refractory to or intolerant of established therapies known to provide clinical benefit.
• •Note: the histologic subtypes that are eligible for enrollment per the 2016 WHO criteria include multiple myeloma(MM), Chronic Lymphoid Leukemias (CLL) , Waldenstrom Macroglobulinemia (WM) primary systemic amyloidosis (PSA), Hodgkin's Lymphoma(HL) and Non-Hodgkin's Lymphoma(NHL).
• •2. Phase Ib, Cohort1 MM Histologically or cytologically confirmed relapsed or refractory multiple myeloma based on WHO diagnosis. Subject has received at least 3 prior anti-myeloma regimens including a proteasome inhibitor (PI), a CD38 antibody and an immunomodulatory agent.
• •* Induction,bone marrow transplant with or without maintenance therapy is considered one regimen.
• •* Refractory is defined as disease that is nonresponsive on therapy, or progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy
• •* For subjects who received more than 1 regimen containing a PI their disease must be refractory to the most recent PI containing regimen.
• •* For subiects who received more than 1 regimen containing an immunomodulatory agent their disease must be refractory to the most recent immunomodulatory agent containing regimen.
• •3. Phase Ib,Cohort DLBCL
• •* Histologically confirmed de novo or transformed DLBCL based on WHO diagnosis , relapsed or refractory to first line chemoimmunotherapy (eg, R-CHOP or equivalent) and second line salvage regimens or autologous hematopoetic cell transplantation, and for whom no further therapy is available that is known to provide clinical benefit.
• •* Disease that is measurable or assessable for response according to Lugano Classification for lymphomas.
• •Note: This may depend on the patient's mutational status, eligibility for allogeneic transplant. Patients must be willing to undergo bone marrow aspirates/biopsies per protocol specifications; These will be performed per protocol schedule to evaluate patient response to treatment.
• •4. ECOG score≤ 2.
• •5. Life expectancy≥ 12 weeks.
• •6. Adequate hepatic function as evidenced by meeting all the following requirements:
• •1. Total bilirubin≤1.5 x upper limit of normal(ULN)or≤3x ULN in patients with documented Gilbert's syndrome;
• •2. Aspartate aminotransferase(AST) and alanine aminotransferase(ALT)≤2.5x ULN; AST or ALT≤5 x ULN if liver metastases are present.
• •7. Renal: serum creatinine≤1.5x ULN or calculated creatinine clearance(CrCL) ≥ 50mL/min (Cockcroft-Gault Formula).
• •8. Hematological function defined as:
• •1. Absolute neutrophil count (ANC)≥ 10x10\^9/L without growth factor support Within 7 days prior to entry;
• •2. Platelet count≥75x10\^9/L without transfusion within 7 days prior to entry;
• •3. Hemoglobin≥ 8g/dL without transfusion within 7 days prior to entry;
• •4. For leukemia: The white blood cell(WBC)count in the patient's peripheral blood must be≤20x10\^9/L within 7 days of the first dose of the study drug. The patients with WBC count\>20x10\^9/L may be treated with hydroxyurea(maximum dose 4g/d) during the Screening period to achieve entry criteria. Hydroxyurea may be continued for the first 5 weeks of treatment(Cycle 1) to control blast counts at the discretion of the Investigator; hydroxyurea must be stopped after the first 5 weeks of treatment. For these patients where is not absolute lower level for neutrophils or platelets for enrollment Platelets and RBCcan be transfused as clinically indicated. Hematopoietic growth factors are prohibited.
• •9. Coagulation tests INR≤ 2 or prothrombin time ≤ 2×ULN.
• •10. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 50% measured by multiple-gated acquisition (MUGA) or echocardiogram (ECHO) or lower limit for institutional normal value.
• •11. Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, Grade ≤2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy.
• •12. Archival tumor tissue will be requested from all patients for exploratory biomarker research. If archival tumor tissue is not available, a fresh biopsy, taken from a readily accessible tumor lesion will be obtained. A patient who does not have a readily accessible tumor may still be enrolled. Tumor tissue is not required for enrollment however an official pathology report documenting the patient's cancer will be required.
• •13. Patients must be willing to undergo transfusion with RBCs and/or platelets if clinically indicated.
• •14. Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use currently accepted reliable contraception method throughout the treatment period and for at least three months following the last dose of study drug. These measures include, but are not limited to, oral or implantable injections of hormonal contraceptives; intrauterine birth control ring or placement of IUS intrauterine device); or use of barrier methods such as condoms or septum and spermicide products. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing age must have a negative pregnancy test.