Back to resultsEfficacy and Safety Study of SyB L-0501 for Patients With Chronic Lymphocytic Leukemia
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
SyB L-0501
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria
Patients meeting all of the following criteria are to be included in the study:
- Patients aged between 20 and 80 years (at the time of registration)
- Patients who have provided written consent in person for participation in this study
- Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
- Patients who are expected to survive for at least 3 months
- Patients who are naive to or not suitable for fludarabine therapy
Patients who are documented with chronic lymphocytic leukemia on the basis of International Workshop on Chronic Lymphocytic Leukaemia guideline (IWCLL) guideline:
- The presence of ≥ 5000/mm3 monoclonal mature B-lymphocytes in the peripheral blood
- ≤ 55 % atypical lymphocytes, prolymphocyte-like cells, and lymphoblasts with prominent nucleoli
- For monoclonal mature B-lymphocytes, at least one of the B-cell specific differentiation antigens (Cluster of differentiation (CD) 19, CD 20, and CD 23) and CD 5 is positive by flow cytometry
Patients in Stage C or stage B with active disease based on Binet staging system (at the time of registration)
- Decision to start treatment should be made upon IWCLL guideline criteria.
Active disease is defined to meet at least one of the following criteria.
- Progression and/or worsening of anemia and/or thrombocytopenia caused by decreased bone marrow function.
- Massive (6 cm below the left costal margin) or progressive or symptomatic splenomegaly
- Massive nodes (≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
- Progressive lymphocytosis with an increase of > 50% over a 2-month period, or lymphocyte doubling time of less than 6 months
- Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
- B symptoms Weight loss > 10% within the previous 6 months Fevers of greater than 38.0° C for 2 or more weeks without other evidence of infection Night sweats
- Patients with 2 or less regimens of previous chemotherapy including antibody therapy. Corticosteroid monotherapy is not counted.
Patients with adequately maintained organ functions (e.g., bone marrow, heart, lung, liver, and kidney functions)
- Neutrophil count: ≥ 1,000 /mm3
- Aspartate aminotransferase(AST) Glutamic oxaloacetic transaminase(GOT): ≤ 3.0 times the upper limit of normal range at each site
- Alanine aminotransferase (ALT) Glutamic pyruvic transaminase(GPT): ≤ 3.0 times the upper limit of normal range at each site
- Total bilirubin: ≤ 1.5 times the upper limit of normal range at each site
- Serum creatinine: ≤ 1.5 times the upper limit of normal range at each site
- Partial pressure of O2 (PaO2): ≥ 65 mmHg
- No abnormalities which require treatment are detected on ECG
- Left ventricular ejection fraction (LVEF) (echocardiography): ≥ 55%
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SyB L-0501
Arm Description
Outcomes
Primary Outcome Measures
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
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.
Absence of significant lymphadenopathy (lymph nodes greater than 1.5 cm in diameter)
No hepatomegaly or splenomegaly
Absence of B symptoms
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
less than 30% of nucleated cells are lymphocytes (confirmed by bone marrow aspiration and no lymphoid nodules).
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
National Cancer Institute-sponsored Working Group (NCI-WG) Response Rate (CR+nPR+PR) Based on IWCLL Guideline
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;
50% or greater reduction in lymphocyte count in peripheral blood from baseline
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
A decrease in the size of the liver and/or spleen by 50% more
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
Complete Remission Rate (CR+CRi) Based on IWCLL Guideline
Progression-free Survival (PFS)
The period from the first day of the study drug administration (Day1) to progressive disease (PD), recurrence/relapse, or death.
Duration of Remission
The period from the day of CR or PR confirmation to recurrence/relapse.
Overall Survival (OS)
The period from the date of patient registration to the date of death.
Adverse Events
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
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
Number of subjects with abnormal or severe values of vital signs, electrocardiogram, and physical examination including ECOG performance status
Full Information
NCT ID
NCT02042911
First Posted
December 17, 2013
Last Updated
December 6, 2016
Sponsor
SymBio Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02042911
Brief Title
Efficacy and Safety Study of SyB L-0501 for Patients With Chronic Lymphocytic Leukemia
Official Title
A Multicenter, Open-label Phase II Study of SyB L-0501 in Patients With Chronic Lymphocytic Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SymBio Pharmaceuticals
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SyB L-0501
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SyB L-0501
Intervention Description
SyB L-0501 is administered at 100 mg/m2/day by intravenous infusion on Day 1 and Day 2 followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 cycles. Dose administration can be delayed or discontinued from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle, but dose reduction is permitted from the 3rd cycle.
Primary Outcome Measure Information:
Title
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
Description
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.
Absence of significant lymphadenopathy (lymph nodes greater than 1.5 cm in diameter)
No hepatomegaly or splenomegaly
Absence of B symptoms
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
less than 30% of nucleated cells are lymphocytes (confirmed by bone marrow aspiration and no lymphoid nodules).
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.
Time Frame
Up to 30 months
Secondary Outcome Measure Information:
Title
National Cancer Institute-sponsored Working Group (NCI-WG) Response Rate (CR+nPR+PR) Based on IWCLL Guideline
Description
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;
50% or greater reduction in lymphocyte count in peripheral blood from baseline
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
A decrease in the size of the liver and/or spleen by 50% more
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
Time Frame
Up to 30 months
Title
Complete Remission Rate (CR+CRi) Based on IWCLL Guideline
Time Frame
Up to 30 months
Title
Progression-free Survival (PFS)
Description
The period from the first day of the study drug administration (Day1) to progressive disease (PD), recurrence/relapse, or death.
Time Frame
Up to 30 months
Title
Duration of Remission
Description
The period from the day of CR or PR confirmation to recurrence/relapse.
Time Frame
Up to 30 months
Title
Overall Survival (OS)
Description
The period from the date of patient registration to the date of death.
Time Frame
Up to 30 months
Title
Adverse Events
Description
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.
Time Frame
Up to 30 months
Title
Number of Subjects With Clinically Significant Laboratory Test Values of Grade 3 or More
Description
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
Time Frame
Up to 30 months
Title
Number of Subjects With Clinically Significant Physical Examination Values
Description
Number of subjects with abnormal or severe values of vital signs, electrocardiogram, and physical examination including ECOG performance status
Time Frame
Up to 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients meeting all of the following criteria are to be included in the study:
Patients aged between 20 and 80 years (at the time of registration)
Patients who have provided written consent in person for participation in this study
Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
Patients who are expected to survive for at least 3 months
Patients who are naive to or not suitable for fludarabine therapy
Patients who are documented with chronic lymphocytic leukemia on the basis of International Workshop on Chronic Lymphocytic Leukaemia guideline (IWCLL) guideline:
The presence of ≥ 5000/mm3 monoclonal mature B-lymphocytes in the peripheral blood
≤ 55 % atypical lymphocytes, prolymphocyte-like cells, and lymphoblasts with prominent nucleoli
For monoclonal mature B-lymphocytes, at least one of the B-cell specific differentiation antigens (Cluster of differentiation (CD) 19, CD 20, and CD 23) and CD 5 is positive by flow cytometry
Patients in Stage C or stage B with active disease based on Binet staging system (at the time of registration)
Decision to start treatment should be made upon IWCLL guideline criteria.
Active disease is defined to meet at least one of the following criteria.
Progression and/or worsening of anemia and/or thrombocytopenia caused by decreased bone marrow function.
Massive (6 cm below the left costal margin) or progressive or symptomatic splenomegaly
Massive nodes (≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
Progressive lymphocytosis with an increase of > 50% over a 2-month period, or lymphocyte doubling time of less than 6 months
Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
B symptoms Weight loss > 10% within the previous 6 months Fevers of greater than 38.0° C for 2 or more weeks without other evidence of infection Night sweats
Patients with 2 or less regimens of previous chemotherapy including antibody therapy. Corticosteroid monotherapy is not counted.
Patients with adequately maintained organ functions (e.g., bone marrow, heart, lung, liver, and kidney functions)
Neutrophil count: ≥ 1,000 /mm3
Aspartate aminotransferase(AST) Glutamic oxaloacetic transaminase(GOT): ≤ 3.0 times the upper limit of normal range at each site
Alanine aminotransferase (ALT) Glutamic pyruvic transaminase(GPT): ≤ 3.0 times the upper limit of normal range at each site
Total bilirubin: ≤ 1.5 times the upper limit of normal range at each site
Serum creatinine: ≤ 1.5 times the upper limit of normal range at each site
Partial pressure of O2 (PaO2): ≥ 65 mmHg
No abnormalities which require treatment are detected on ECG
Left ventricular ejection fraction (LVEF) (echocardiography): ≥ 55%
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Toshihiko Nagase
Organizational Affiliation
SymBio Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Research Site
City
Fukuyama
State/Province
Hiroshima
Country
Japan
Facility Name
Research Site
City
Isehara
State/Province
Kanagawa
Country
Japan
Facility Name
Research Site
City
Izumo
State/Province
Shimane
Country
Japan
Facility Name
Research Site
City
Minato-ku
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Kagoshima
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety Study of SyB L-0501 for Patients With Chronic Lymphocytic Leukemia
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