Study of SyB L-0501 to Treat Relapsed/Refractory Multiple Myeloma

• Sponsor: SymBio Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01849848
• Collaborator: (none)
• Enrollment: 17
• Locations: 14
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the antitumor efficacy and safety of bendamustine (SyB L-0501: 90 mg/m^2/day) for a maximum of 6 cycles (1 cycle: intravenous administration for 2 consecutive days and 26-day observation period) in patients with relapsed/refractory multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Multiple Myeloma	Drug: SyB L-0501	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label Phase II Study of SyB L-0501 in Patients With Relapsed/Refractory Multiple Myeloma
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SyB L-0501	Drug: SyB L-0501; The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.

Outcome Measures

Primary Outcome Measures

1. Response Rate [Stringent CR (sCR)+Complete Response (CR)+Very Good PR (VGPR)+Partial Response (PR)]Based on International Myeloma Working Group (IMWG) Criteria [up to around 44 weeks]

   The criteria for sCR, CR, VGPR, and PR based on IMWG are shown below. sCR: Fulfills CR criteria as well as all of the following conditions Normal free light chain (FLC) ratio(κ/λ) Disappearance of clonal cells in bone marrow by immunohistochemistry or immunofluorescence CR: Fulfills all of the following criteria Negative immunofixation of serum and urine M-protein <5% plasma cells in bone marrow Disappearance of any soft tissue plasmacytoma VGPR: Fulfills at least one of the following criteria Serum and urine M-protein detectable by immunofixation but not electrophoresis ≥90% reduction in serum M-protein and 24-hour M-protein excretion amount in urine <0.1 g/24 hour PR: Fulfills the following criteria ≥50% reduction in serum M-protein, and ≥90% reduction in urine M-protein, urine M-protein excretion amount is reduced to < 0.2 g/24hours

Secondary Outcome Measures

1. Response Rate (sCR+CR) Based on IMWG Criteria [up to around 44 weeks]

2. Complete Response (CR) Based on the Blade Criteria [up to around 44 weeks]

   The criteria for CR based on the Blade are shown below. CR requires all of the followings: Absence of the original monoclonal paraprotein in serum and urine by immunofixation, maintained for a minimum of 6 weeks <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas

3. Response Rate (CR+PR) Based on the Blade Criteria [up to around 44 weeks]

   The criteria for PR based on the Blade are shown below. PR requires 1. or all of the others: Some, but not all, of the criteria for CR are fulfilled ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks Reduction in 24 h urinary light chain excretion either by ≥90% or to <200 mg, maintained for a minimum of 6 weeks For patients with non-secretory myeloma only, ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy ≥50% reduction in the size of soft tissue plasmacytomas No increase in size or number of lytic bone lesions

4. Progression-Free Survival (PFS) [up to around 44 weeks]

   Using the registration date as the start date, PFS with relapse/recurrence or progression, and death regardless of the cause as events are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and the 95% confidence interval are to be calculated.

5. Time to Treatment Failure (TTF) [up to around 44 weeks]

   Using the registration date as the start date, TTF with relapse/recurrence or progression, death regardless of the cause, and early discontinuation of treatment as events are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and 95% confidence interval are to be calculated.

6. Duration of Response (DOR) [up to around 44 weeks]

   From initial response (PR or higher), DOR with relapse/recurrence or progression, and death, regardless of cause, as events, are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and 95% confidence interval are to be calculated.

7. Overall Survival (OS) [up to around 44 weeks]

   Using the registration date as the start date, OS with death, regardless of the cause, as events, are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and 95% confidence interval are to be calculated.

8. Adverse Events [up to around 44 weeks]

   All adverse events occurring during the administration of the investigational product are to be examined for safety by cross tabulation lists and tables of incidence from the viewpoint of relationship with the drug, disease severity and medicine treated group.

9. Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values [up to around 44 weeks]

   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

10. Number of Abnormalities (Grade ≥3) in Laboratory Test Values [up to around 44 weeks]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 79 Years
• Sexes Eligible for Study: All

Inclusion Criteria:

1. Patients who are diagnosed with multiple myeloma on the basis of the response criteria of the International Myeloma Working Group (IMWG) and confirmed to meet one or more of the following criteria:

(definition of progression according to the IMWG response criteria)

• 25% or more increase compared to baseline for the following values

• Serum M-protein level (however, the absolute value is 0.5 g/dL or higher)

• Urine M-protein level (however, absolute value is 200 mg/24 hours or higher)

• For lesions without measurable serum or urine M-protein values. involved/uninvolved free light chain (FLC) ratio (however, absolute value is 10 mg/dL or higher)

• Clear appearance of new bone lesions or soft tissue plasmacytoma or apparent growth in size of current bone lesions or soft tissue plasmacytoma

• Appearance of hypercalcemia (corrected calcium level ≥ 11.5 mg/dL and if determined to be caused solely by myelomas)

1. Patients with measurable lesions (meets at least one of the following two criteria

• Serum M-protein [Immunoglobulin G (IgG)≥ 1.0 g/dL, Immunoglobulin A (IgA) ≥ 0.5 g/dL, Immunoglobulin D (IgD) ≥ 0.1 g/dL)

• Urine M-protein ≥ 200 mg/24 hours

1. Patients who meet either one of the following items for all prior chemotherapy using proteasome inhibitors, Immunomodulatory Drugs (IMiDs) (thalidomide or lenalidomide) or alkylating agents.

• No response*

• Relapse/recurrence after response*

• Intolerance

• Not applicable (reason can be confirmed in the source document) because of predicted aggravation of complications (neurotoxicity, etc.) * Patients whose disease has progressed based on the IMWG response criteria after receiving the most recent therapy

1. Patients who have undergone a washout period of more than 3 weeks after the end of the previous therapy and determined not to be under the effect of previous treatment (antitumor effectiveness).

2. Patients who are expected to survive for at least 3 months

3. Patients aged from 20 to 79 years at the time of interim registration

4. Performance Status (P.S.) of 0 to 125. However, P.S. 2 due to pain from lytic bone lesions is acceptable

5. Patients with adequately maintained organ functions (e.g., bone marrow, heart, lung, liver, and kidney functions)

• Neutrophil count:≥ 1,500 /mm^3

• Platelet count:≥ 75,000 /mm^3

• Albumin:≥ 2.5 g /dL

• Aspartate aminotransferase (AST) Glutamic oxaloacetic transaminase (GOT): < than 3.0 times the upper limit of normal range for the site

• Alanine aminotransferase (ALT) Glutamic pyruvic transaminase (GPT): < than 3.0 times the upper limit of normal range for the site

• Total bilirubin: < than 1.5 times the upper limit of normal range for the site

• Serum creatinine: < than 3.0 times the upper limit of normal range for the site

• Partial pressure of O2 (PaO2) ≥ 65 mmHg

• No abnormalities which require treatment are detected on ECG

• Left ventricular ejection fraction (LVEF)(echocardiography): ≥ 55%

1. Patients who have provided written consent for participation in this study

Exclusion Criteria:

1. Patients with apparent infections (including viral infections)

2. Patients with serious complications (hepatic or renal dysfunction, etc.)

3. Patients with complications or medical history of serious cardiac disease (e.g., myocardial infarction, ischemic heart disease) within 2 years of the date of interim registration or patients with arrhythmias that require treatment

4. Patients with serious gastrointestinal symptoms (e.g., severe nausea, vomiting, or diarrhea)

5. Patients positive for Hepatitis B surface (HBs) antigen, Hepatitis C virus (HCV) antibody, or HIV antibody

6. Patients with serious bleeding tendencies (e.g., disseminated intravascular coagulation: DIC)

7. Patients with, or confirmed in the past to have had, interstitial pneumonia, pulmonary fibrosis, or pulmonary emphysema which requires treatment.

8. Patients with a complication of apparent cardiac amyloidosis

9. Patients with infiltration to the central nervous system (CNS) or patients with clinical symptoms of suspected infiltration to the CNS,

10. Patients with active multiple primary cancer

11. Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia

12. Patients who have received this investigational product in the past

13. Patients who have received allogeneic stem cell transplants in the past. (patients who have received autologous stem cell transplantation are acceptable)

14. Patients who received cytokine preparations such as erythropoietin or granulocyte colony stimulating factor (G-CSF) or blood transfusions within 1 week prior to the examination conducted before interim registration for this study

15. Patients who received other investigational products or unapproved medications within 3 months before interim registration for this study

16. Patients with prior allergies to medications that are similar to this investigational product (e.g., alkylating agents, or purine-nucleoside derivatives) or mannitol

17. Patients with drug addiction, narcotics addiction, and/or alcohol dependency

18. Patients who are pregnant, who may possibly be pregnant, or lactating

19. Patients who do not agree to practice contraception for the following periods:

Male: During investigational product administration and until 6 months after final administration Female: During investigational product administration and until 4 months after final administration

1. Patients otherwise judged by the investigator or sub-investigator to be unsuitable for inclusion in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chuo-ku		Japan
2		Fukuoka		Japan
3		Isehara		Japan
4		Koto-ku		Japan
5		Kyoto		Japan
6		Nagoya		Japan
7		Niigata		Japan
8		Okayama		Japan
9		Sapporo		Japan
10		Sendai		Japan
11		Shibukawa		Japan
12		Shibuya-ku		Japan
13		Tokushima		Japan
14		Utsunomiya		Japan

Sponsors and Collaborators

• SymBio Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SymBio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01849848
• Other Study ID Numbers: 2011004
• First Posted: May 9, 2013
• Last Update Posted: Feb 6, 2015
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

Participant Flow

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Period Title: Overall Study
STARTED	17
COMPLETED	13
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Overall Participants	17
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.5 (9.8)
Age, Customized (participants) [Number]
20-29 years	0 0%
30-39 years	0 0%
40-49 years	2 11.8%
50-59 years	3 17.6%
60-69 years	7 41.2%
70-79 years	5 29.4%
Sex: Female, Male (Count of Participants)
Female	5 29.4%
Male	12 70.6%
Subtype of myeloma (participants) [Number]
Immunoglobulin G	10 58.8%
Immunoglobulin A	6 35.3%
Immunoglobulin D	0 0%
Bence Jones type	8 47.1%
κ	13 76.5%
λ	4 23.5%
Prior therapy (participants) [Number]
Absent	0 0%
Present	17 100%
Proteasome inhibitor	17 100%
IMIDs	16 94.1%
Alkylating agent	17 100%
Other	11 64.7%
Performance status (participants) [Number]
0	7 41.2%
1	8 47.1%
2	2 11.8%
Clinical disease stage (International Staging System) (participants) [Number]
I	3 17.6%
II	11 64.7%
III	3 17.6%
Medical history (participants) [Number]
Absent	10 58.8%
Present	7 41.2%
Accompanying symptoms of the primary disease (participants) [Number]
Absent	1 5.9%
Present	16 94.1%
Complication (participants) [Number]
Absent	0 0%
Present	17 100%
Serum β2 microglobulin (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	4.03 (1.59)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	159.05 (9.95)
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	56.86 (10.06)
Body surface area (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.576 (0.181)

Outcome Measures

1. Primary Outcome

Title	Response Rate [Stringent CR (sCR)+Complete Response (CR)+Very Good PR (VGPR)+Partial Response (PR)]Based on International Myeloma Working Group (IMWG) Criteria
Description	The criteria for sCR, CR, VGPR, and PR based on IMWG are shown below. sCR: Fulfills CR criteria as well as all of the following conditions Normal free light chain (FLC) ratio(κ/λ) Disappearance of clonal cells in bone marrow by immunohistochemistry or immunofluorescence CR: Fulfills all of the following criteria Negative immunofixation of serum and urine M-protein <5% plasma cells in bone marrow Disappearance of any soft tissue plasmacytoma VGPR: Fulfills at least one of the following criteria Serum and urine M-protein detectable by immunofixation but not electrophoresis ≥90% reduction in serum M-protein and 24-hour M-protein excretion amount in urine <0.1 g/24 hour PR: Fulfills the following criteria ≥50% reduction in serum M-protein, and ≥90% reduction in urine M-protein, urine M-protein excretion amount is reduced to < 0.2 g/24hours
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Number (95% Confidence Interval) [percentage of paticipants]	0

2. Secondary Outcome

Title	Response Rate (sCR+CR) Based on IMWG Criteria
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Number (95% Confidence Interval) [percentage of paticipants]	0

3. Secondary Outcome

Title	Complete Response (CR) Based on the Blade Criteria
Description	The criteria for CR based on the Blade are shown below. CR requires all of the followings: Absence of the original monoclonal paraprotein in serum and urine by immunofixation, maintained for a minimum of 6 weeks <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Number (95% Confidence Interval) [percentage of paticipants]	0

4. Secondary Outcome

Title	Response Rate (CR+PR) Based on the Blade Criteria
Description	The criteria for PR based on the Blade are shown below. PR requires 1. or all of the others: Some, but not all, of the criteria for CR are fulfilled ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks Reduction in 24 h urinary light chain excretion either by ≥90% or to <200 mg, maintained for a minimum of 6 weeks For patients with non-secretory myeloma only, ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy ≥50% reduction in the size of soft tissue plasmacytomas No increase in size or number of lytic bone lesions
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Number (95% Confidence Interval) [percentage of paticipants]	0

5. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Using the registration date as the start date, PFS with relapse/recurrence or progression, and death regardless of the cause as events are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and the 95% confidence interval are to be calculated.
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Median (95% Confidence Interval) [Days]	92.0

6. Secondary Outcome

Title	Time to Treatment Failure (TTF)
Description	Using the registration date as the start date, TTF with relapse/recurrence or progression, death regardless of the cause, and early discontinuation of treatment as events are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and 95% confidence interval are to be calculated.
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Median (95% Confidence Interval) [Days]	71.0

7. Secondary Outcome

Title	Duration of Response (DOR)
Description	From initial response (PR or higher), DOR with relapse/recurrence or progression, and death, regardless of cause, as events, are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and 95% confidence interval are to be calculated.
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Median (95% Confidence Interval) [Days]	NA

8. Secondary Outcome

Title	Overall Survival (OS)
Description	Using the registration date as the start date, OS with death, regardless of the cause, as events, are to be summarized using the Kaplan-Meier estimator and the 50% point according to the Greenwood's formula and 95% confidence interval are to be calculated.
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Median (95% Confidence Interval) [Days]	243.0

9. Secondary Outcome

Title	Adverse Events
Description	All adverse events occurring during the administration of the investigational product are to be examined for safety by cross tabulation lists and tables of incidence from the viewpoint of relationship with the drug, disease severity and medicine treated group.
Time Frame	up to around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
Any adverse event	17 100%
Adverse drug reaction	17 100%
SAE	4 23.5%
Death	0 0%
Discontinuation due to adverse events	1 5.9%

10. Secondary Outcome

Title	Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values
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 around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
CD4 lymphocytes decreased	13 76.5%
Electrocardiogram QT corrected interval prolonged	1 5.9%
Investigations - Other, sodium decreased	2 11.8%
Investigations - Other, potassium decreased	1 5.9%
Investigations - Other, calcium increased	1 5.9%
Investigations - Other, Haemoglobin decreased	2 11.8%
Lymphocyte count decreased	16 94.1%
Neutrophil count decreased	11 64.7%
Platelet count decreased	2 11.8%
Weight increased	1 5.9%
White blood cell decreased	12 70.6%

11. Secondary Outcome

Title	Number of Abnormalities (Grade ≥3) in Laboratory Test Values
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 around 44 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
Measure Participants	17
CD4 lymphocytes decreased	14
Electrocardiogram QT corrected interval prolonged	1
Investigations - Other, sodium decreased	2
Investigations - Other, potassium decreased	2
Investigations - Other, calcium increased	1
Investigations - Other, Haemoglobin decreased	2
Lymphocyte count decreased	33
Neutrophil count decreased	15
Platelet count decreased	3
Weight increased	1
White blood cell decreased	17

Adverse Events

Time Frame	up to around 44 weeks
Arm/Group Title	SyB L-0501
Arm/Group Description	SyB L-0501: The administration of SyB L-0501 at 90 mg/m^2/day by 60-minute intravenous infusion for 2 consecutive days followed by 26 days of monitoring. This is considered to be one cycle and may be repeated up to 6 times. Dose reduction or discontinuation is permitted from the second cycle as necessary according to adverse events and the results of monitoring during the previous cycle.
All Cause Mortality
	SyB L-0501
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SyB L-0501
	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)
Gastrointestinal disorders
Constipation	1/17 (5.9%)
Infections and infestations
Pneumonia	1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/17 (5.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma	1/17 (5.9%)
Other (Not Including Serious) Adverse Events
	SyB L-0501
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anaemia	7/17 (41.2%)
Eye disorders
Conjunctivitis	1/17 (5.9%)
Dry eye	1/17 (5.9%)
Gastrointestinal disorders
Abdominal pain	1/17 (5.9%)
Constipation	5/17 (29.4%)
Dental caries	1/17 (5.9%)
Diarrhoea	3/17 (17.6%)
Haemorrhoids	1/17 (5.9%)
Nausea	8/17 (47.1%)
Proctalgia	1/17 (5.9%)
Stomatitis	1/17 (5.9%)
Vomiting	2/17 (11.8%)
Dyschezia	1/17 (5.9%)
General disorders
Asthenia	1/17 (5.9%)
Chest pain	1/17 (5.9%)
Gait disturbance	1/17 (5.9%)
Generalised oedema	2/17 (11.8%)
Injection site reaction	4/17 (23.5%)
Malaise	4/17 (23.5%)
Oedema peripheral	4/17 (23.5%)
Pyrexia	3/17 (17.6%)
Injection site vasculitis	1/17 (5.9%)
Hepatobiliary disorders
Hepatic function abnormal	1/17 (5.9%)
Infections and infestations
Bronchopneumonia	1/17 (5.9%)
Nasopharyngitis	2/17 (11.8%)
Periodontitis	1/17 (5.9%)
Pharyngitis	1/17 (5.9%)
Pneumonia	1/17 (5.9%)
Injury, poisoning and procedural complications
Fall	1/17 (5.9%)
Fracture	1/17 (5.9%)
Spinal compression fracture	1/17 (5.9%)
Investigations
Alanine aminotransferase increased	4/17 (23.5%)
Aspartate aminotransferase increased	5/17 (29.4%)
Blood albumin decreased	2/17 (11.8%)
Blood calcium increased	2/17 (11.8%)
Blood chloride decreased	2/17 (11.8%)
Blood creatinine increased	3/17 (17.6%)
Blood lactate dehydrogenase increased	2/17 (11.8%)
Blood potassium decreased	2/17 (11.8%)
Blood pressure decreased	1/17 (5.9%)
Blood sodium decreased	3/17 (17.6%)
Blood urea increased	2/17 (11.8%)
Blood uric acid decreased	2/17 (11.8%)
Blood uric acid increased	1/17 (5.9%)
C-reactive protein increased	5/17 (29.4%)
CD4 lymphocytes decreased	13/17 (76.5%)
Electrocardiogram QT prolonged	1/17 (5.9%)
Gamma-glutamyltransferase increased	2/17 (11.8%)
Blood urine present	4/17 (23.5%)
Haemoglobin decreased	7/17 (41.2%)
Lymphocyte count decreased	16/17 (94.1%)
Neutrophil count decreased	16/17 (94.1%)
Neutrophil count increased	2/17 (11.8%)
Platelet count decreased	12/17 (70.6%)
Protein total decreased	1/17 (5.9%)
Protein total increased	1/17 (5.9%)
Red blood cell count decreased	5/17 (29.4%)
Weight decreased	6/17 (35.3%)
Weight increased	1/17 (5.9%)
White blood cell count decreased	17/17 (100%)
White blood cell count increased	2/17 (11.8%)
Protein urine present	2/17 (11.8%)
Blood alkaline phosphatase increased	1/17 (5.9%)
Urine output decreased	1/17 (5.9%)
Metabolism and nutrition disorders
Hyperkalaemia	3/17 (17.6%)
Hyperuricaemia	1/17 (5.9%)
Hypoalbuminaemia	2/17 (11.8%)
Hypochloraemia	1/17 (5.9%)
Hypokalaemia	1/17 (5.9%)
Hypophosphataemia	1/17 (5.9%)
Decreased appetite	4/17 (23.5%)
Hyponatraemia	3/17 (17.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/17 (11.8%)
Back pain	5/17 (29.4%)
Bone pain	2/17 (11.8%)
Muscle haemorrhage	1/17 (5.9%)
Musculoskeletal pain	2/17 (11.8%)
Myalgia	1/17 (5.9%)
Neck pain	1/17 (5.9%)
Nervous system disorders
Dysgeusia	1/17 (5.9%)
Headache	2/17 (11.8%)
Neuropathy peripheral	1/17 (5.9%)
Somnolence	1/17 (5.9%)
Psychiatric disorders
Delirium	1/17 (5.9%)
Insomnia	3/17 (17.6%)
Renal and urinary disorders
Renal failure	1/17 (5.9%)
Renal impairment	2/17 (11.8%)
Dysuria	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Hiccups	2/17 (11.8%)
Hypoxia	1/17 (5.9%)
Upper respiratory tract inflammation	2/17 (11.8%)
Pharyngeal erythema	1/17 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia	1/17 (5.9%)
Decubitus ulcer	1/17 (5.9%)
Dermatitis contact	1/17 (5.9%)
Pruritus	4/17 (23.5%)
Rash	2/17 (11.8%)
Surgical and medical procedures
Tooth extraction	1/17 (5.9%)
Vascular disorders
Hypertension	2/17 (11.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.