Efficacy and Safety Study of SyB L-0501 for Patients With Chronic Lymphocytic Leukemia

Phase 2

Completed

Conditions: Chronic Lymphocytic Leukemia

Interventions: Drug: SyB L-0501

Registration Number: NCT02042911

Lead Sponsor: SymBio Pharmaceuticals

Brief Summary: The purpose of this study is to investigate safety and efficacy of SyB L-0501 after 2-day intravenous infusion at a dose of 100 mg/m2/day to patients with chronic lymphocytic leukemia.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Patients who fall under any one of the following criteria are to be excluded

Patients who have been without treatment for less than 4 weeks after prior treatment. For patients treated with antibody therapy or underwent hematopoietic stem cell transplantation, for 3 months after prior treatment
Patients who enrolled other clinical studies within 4 weeks before registration for this study
Patients who received allogeneic stem cell transplantation in the past
Patients with defective p53 (17p-) confirmed by chromosome analysis (Fluorescence in situ hybridization (Fish) method)
Patients who are clinically diagnosed with Richter's syndrome
Patients with infiltration to the central nervous system (CNS) or patients with clinical symptoms of suspected infiltration to the CNS
Patients with multiple primary cancers or patients with a history of other malignant tumors within past 5 years, except for basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or gastrointestinal tract
Patients with serious bleeding tendencies (e.g., disseminated intravascular coagulation (DIC))
Patients with, or confirmed in the past to have had, interstitial lung disease or pulmonary fibrosis
Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia responds to corticosteroid therapy
Patients with any of the following complications
- serious cardiac disease (e.g., myocardial infarction, ischemic heart disease, or arrhythmia requiring treatment)
- serious, active infections (requiring intravenous administration of antibiotics, antifungal drugs, or antiviral drugs)
- hepatic or renal dysfunction
- accumulation of pleural effusion, pericardial effusion, or peritoneal effusion
- uncontrollable serious gastrointestinal disease, endocrine disorder, or mental illness
Patients who received SyB L-0501 in the past
Patients with allergies to mannitol
Patients who need cytokine preparations such as erythropoietin or granulocyte colony stimulating factor (G-CSF) or blood transfusions at registration for this study
Patients positive for HIV antibody or Hepatitis C virus (HCV) antibody
Patients positive for Hepatitis B surface (HBs) antigen. Patients with negative results will also be checked for Hepatitis B core (HBc) antibody and HBs antibody. If either of the test results is positive, measure Hepatitis B virus (HBV)-DNA and exclude the patients with results above sensitivity
Patients with clinical symptom of cytomegalovirus (CMV) infection, except asymptomatic patients with CMV positive
Patients who are pregnant, who may possibly be pregnant, or lactating
Patients who do not agree to practice contraception. Male: During investigational product administration and until 6 months after final administration Female: During investigational product administration and until 4 months after final administration
Patients with drug addiction, narcotics addiction, and/or alcohol dependency
Patients otherwise judged by the investigator or sub-investigator to be unsuitable for inclusion in this study

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SyB L-0501	SyB L-0501	-

Primary Outcome Measures

Name	Time	Method
Response Rate [Complete Remission (CR) +Complete Remission / Incomplete (CRi) + Nodular Partial Remission (nPR) + Partial Remission (PR)] Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guideline	Up to 30 months	The criteria for CR, CRi, nPR and PR based on IWCLL guideline are shown below. For the criteria for nPR and PR, please refer to the description of NCI-WG response rate (CR+nPR+PR). CR: Assessment should be made at least 8 weeks after completion of administration. 1. Absence of significant lymphadenopathy (lymph nodes greater than 1.5 cm in diameter) 2. No hepatomegaly or splenomegaly 3. Absence of B symptoms 4. Meet the following laboratory test values; * lymphocyte count in peripheral blood: \<4.0×10\^9/L * neutrophil count: \>1.5×10\^9/L * platelet count: 100×10\^9/L * hemoglobin: 11.0 g/dL without transfusions 5. less than 30% of nucleated cells are lymphocytes (confirmed by bone marrow aspiration and no lymphoid nodules). 6. No new lesion emergence CRi: Fulfills all of the following criteria * Delayed anemia, thrombocytopenia, or neutropenia is observed. * Fulfills all CR criteria other than 4). * Delayed symptoms are all judged to be caused by drug.

Secondary Outcome Measures

Name	Time	Method
Duration of Remission	Up to 30 months	The period from the day of CR or PR confirmation to recurrence/relapse.
Overall Survival (OS)	Up to 30 months	The period from the date of patient registration to the date of death.
Adverse Events	Up to 30 months	All undesirable medical events experienced by the subject treated with the investigational product (including abnormal changes in laboratory values) are treated as adverse events and evaluated for safety.
Number of Subjects With Clinically Significant Laboratory Test Values of Grade 3 or More	Up to 30 months	Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using Common Terminology Criteria for Adverse Events (CTCAE). grade 1 : mild grade 2 : moderate grade 3 : severe or medically significant but not immediately life-threatening grade 4 : life threatening or disabling grade 5 : death related to adverse event
Number of Subjects With Clinically Significant Physical Examination Values	Up to 30 months	Number of subjects with abnormal or severe values of vital signs, electrocardiogram, and physical examination including ECOG performance status
Complete Remission Rate (CR+CRi) Based on IWCLL Guideline	Up to 30 months
National Cancer Institute-sponsored Working Group (NCI-WG) Response Rate (CR+nPR+PR) Based on IWCLL Guideline	Up to 30 months	The criteria for nPR and PR based on IWCLL guideline are shown below. nPR: Fulfills all CR criteria other than residual lymphoid nodules confirmed by bone marrow examination. PR: Fulfills two or more items from Group A and one or more items from Group B for a minimal duration of 8 weeks. Group A; 1. 50% or greater reduction in lymphocyte count in peripheral blood from baseline 2. 50% or greater reduction (size reduction) in Sum of the products of the greatest diameters (SPD) and no new lesion emergence or no new enlarged lymph node 3. A decrease in the size of the liver and/or spleen by 50% more 4. A decrease in marrow infiltration or lymphoid nodules by 50% more Group B; 1) Neutrophil count \>1.5×10\^9/L or 50% improvement from baseline 2) Platelet count \>100×10\^9/L or 50% improvement from baseline 3) Hemoglobin 11.0 g/dL or 50% improvement from baseline without transfusions
Progression-free Survival (PFS)	Up to 30 months	The period from the first day of the study drug administration (Day1) to progressive disease (PD), recurrence/relapse, or death.