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The study objectives of this study are to determine the effects, safety, and pharmacokinetics of bendamustine for multiple myeloma to a regimen of bendamustine and prednisolone.
The study objectives of this study are to determine the effects, safety, and pharmacokinetics of bendamustine for untreated and maladjustment to hematopoietic stem cell transplantation (HSCT) multiple myeloma to a regimen of bendamustine and prednisolone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SyB L-0501 + prednisolone | Experimental | SyB L-0501 (150 mg/m2/day) will be administered by intravenous drip infusion for 60 min for 2 consecutive days and the course will be observed for the next 26 days. This is taken as one cycle and administration is repeated for 2-9 cycles (when a plateau is not reached after nine cycles, administration of up to an additional three cycles for a maximum of 12 cycles is possible. Prednisolone (60 mg/m2/day) will be administered orally for 4 consecutive days and the course will be observed for the next 24 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SyB L-0501 | Drug | SyB L-0501 (150 mg/m2/day) will be administered by intravenous drip infusion for 60 min for 2 consecutive days and the course will be observed for the next 26 days. This is taken as one cycle and administration is repeated for 2-9 cycles (when a plateau is not reached after nine cycles, administration of up to an additional three cycles for a maximum of 12 cycles is possible). |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response (CR) Rate [Based on the Modified Southwest Oncology Group (SWOG) Criteria] | The proportion of subjects evaluated as CR was calculated. CR (modified SWOG) requires all of the followings:
| Up to 36 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| CR Rate [Based on the International Myeloma Working Group (IMWG) Criteria] | The proportion of subjects evaluated as CR [strict CR (sCR) + CR] was calculated. sCR (IMWG): CR as defined below plus Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence CR (IMWG): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow |
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Inclusion Criteria:
Patients are included in the study if all of the following criteria are met: Patients confirmed to have multiple myeloma (symptomatic myeloma) defined in the diagnostic criteria of the International Myeloma Working Group (IMWG).
Exclusion Criteria:
Patients are excluded from participating in the study if 1 or more of the following criteria are met:
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| Name | Affiliation | Role |
|---|---|---|
| Shinsuke Iida, MD, Ph D | Nagoya City University Graduate School of Medical Sciences | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research site | Nagoya | Aichi-ken | Japan | |||
| Research site |
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| ID | Title | Description |
|---|---|---|
| FG000 | SyB L-0501 + Prednisolone | SyB L-0501 (150 mg/m2/day) will be administered by intravenous drip infusion for 60 min for 2 consecutive days and the course will be observed for the next 26 days. This is taken as one cycle and administration is repeated for 2-9 cycles (when a plateau is not reached after nine cycles, administration of up to an additional three cycles for a maximum of 12 cycles is possible. Prednisolone (60 mg/m2/day) will be administered orally for 4 consecutive days and the course will be observed for the next 24 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | SyB L-0501 + Prednisolone | SyB L-0501 (150 mg/m2/day) will be administered by intravenous drip infusion for 60 min for 2 consecutive days and the course will be observed for the next 26 days. This is taken as one cycle and administration is repeated for 2-9 cycles (when a plateau is not reached after nine cycles, administration of up to an additional three cycles for a maximum of 12 cycles is possible. Prednisolone (60 mg/m2/day) will be administered orally for 4 consecutive days and the course will be observed for the next 24 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete Response (CR) Rate [Based on the Modified Southwest Oncology Group (SWOG) Criteria] | The proportion of subjects evaluated as CR was calculated. CR (modified SWOG) requires all of the followings:
| Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 36 weeks |
|
Up to 2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SyB L-0501 + Prednisolone | SyB L-0501 (150 mg/m2/day) will be administered by intravenous drip infusion for 60 min for 2 consecutive days and the course will be observed for the next 26 days. This is taken as one cycle and administration is repeated for 2-9 cycles (when a plateau is not reached after nine cycles, administration of up to an additional three cycles for a maximum of 12 cycles is possible. Prednisolone (60 mg/m2/day) will be administered orally for 4 consecutive days and the course will be observed for the next 24 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (14.1) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.1) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Toshihiko Nagase | Symbio Pharmaceuticals | 81-3-5472-1127 | tnagase.331@symbiopharma.com |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D011239 | Prednisolone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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|
| prednisolone | Drug | Prednisolone will be administered (60 mg/m2/day) orally for 4 consecutive days and the course will be observed for the next 24 days. |
|
| Up to 36 weeks |
| Response Rate (Based on the IMWG Criteria) | The proportion of subjects evaluated as response [sCR + CR + very good partial response (VGPR) + Partial Response (PR)] was calculated. VGPR (IMWG): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 h PR (IMWG): ≥50% reduction of serum M-protein and reduction in 24 h urinary M-protein by ≥90% or to <200mg per 24 h | Up to 36 weeks |
| CR Rate Based on the (Bladé) Criteria | The proportion of subjects evaluated as CR was calculated. CR (Bladé) requires all of the followings:
| Up to 36 weeks |
| Response Rate (Based on the Bladé Criteria) | The proportion of subjects evaluated as response (CR + PR) was calculated. PR (Bladé) requires 1. or all of the others:
| Up to 36 weeks |
| Response Rate (Based on the Modified SWOG Criteria) | The proportion of subjects evaluated as response (CR + PR) was calculated. PR (SWOG) requires the followings:
| Up to 36 weeks |
| Progression-Free Survival (PFS) | PFS is the period from patient registration to either the date of recurrence, exacerbation, progression or death. Recurrence, exacerbation, progression were assessed from serum M-protein, urine M-protein, serum free light chain (FLC), the percentage of marrow plasma cells, disappearance of clonal plasma cells, plasma cell tumor in soft tissue, and bone lesion. | Up to 2 years |
| Time to Treatment Failure (TTF) | TTF is the period from patient registration to either the date of recurrence, exacerbation, progression, death or discontinuation of treatment. | Up to 2 years |
| Duration of Response (DOR) | DOR is the period from the date of achieving CR or PR to either the date of recurrence, exacerbation, progression or death. | Up to 2 years |
| Overall Survival (OS) | OS is the period from the date of patient registration to the date of death. | Up to 2 years |
| Number of Subjects With Adverse Event, Related Adverse Event, Serious Adverse Event, and Related Serious Adverse Event | Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.02, Japan Clinical Oncology Group/Japan Society of Clinical Oncology (JCOG/JSCO) version, and were encoded using Medical Dictionary for Regulatory Activities (MedDRA). | Up to 2 years |
| Number of Adverse Events, Related Adverse Events, Serious Adverse Events, and Related Serious Adverse Events | Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.02, Japan Clinical Oncology Group/Japan Society of Clinical Oncology (JCOG/JSCO) version, and were encoded using Medical Dictionary for Regulatory Activities (MedDRA). | Up to 2 years |
| Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values | Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using 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 AE | Up to 2 years |
| Number of Abnormalities (Grade ≥3) in Laboratory Test Values | Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using CTCAE. | Up to 2 years |
| Pharmacokinetic Parameters (Cmax) | Plasma pharmacokinetics (Cmax) of unchanged bendamustine | On Day 1 only |
| Pharmacokinetic Parameters (Tmax) | Plasma pharmacokinetics (tmax) of unchanged bendamustine | On Day 1 only |
| Pharmacokinetic Parameters (AUC) | Plasma pharmacokinetics (AUC) of unchanged bendamustine | On Day 1 only |
| Pharmacokinetic Parameters (t1/2) | Plasma pharmacokinetics (t1/2) of unchanged bendamustine | On Day 1 only |
| Fukuoka |
| Fukuoka |
| Japan |
| Research site | Isehara | Kanagawa | Japan |
| Year |
|
| Age, Customized | Number | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Condition with symptoms of Multiple Myeloma | Condition with symptoms of Multiple Myeloma (Development of hyperviscosity syndrome, amyloidosis, Bacterial infection twice or more in a year) | Number | Participants |
|
| Previous treatment of multiple myeloma | Number | Participants |
|
| Reason for not eligible for hematopoietic stem cell transplantation | Number | Participants |
|
| Performance status (P.S.) | 0: Asymptomatic 1: Symptomatic but completely ambulatory 2: Symptomatic, <50% in bed during the day 3: Symptomatic, >50% in bed, but not bedbound | Number | Participants |
|
| Clinical stage [International staging system (ISS) category] | Stage I: Serum β2-microglobulin (β2M) < 3.5 mg/L and serum albumin ≥ 3.5 g/dL) Stage II: Serum β2M ≥3.5 - < 5.5 mg/L; or serum β2M < 3.5 mg/L and serum albumin < 3.5 g/dL) Stage III: (Serum β2M ≥ 5.5 mg/L) | Number | Participants |
|
| Previous history of multiple myeloma | Number | Participants |
|
| Associated symptom of the primary disease | Number | Participants |
|
| Complications of multiple myeloma | Number | Participants |
|
| Serum β2M in clinical stage | Median | Standard Deviation | mg/L |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Median | Standard Deviation | kg |
|
| Body surface area | Median | Standard Deviation | m2 |
|
|
|
| Secondary | CR Rate [Based on the International Myeloma Working Group (IMWG) Criteria] | The proportion of subjects evaluated as CR [strict CR (sCR) + CR] was calculated. sCR (IMWG): CR as defined below plus Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence CR (IMWG): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 36 weeks |
|
|
|
| Secondary | Response Rate (Based on the IMWG Criteria) | The proportion of subjects evaluated as response [sCR + CR + very good partial response (VGPR) + Partial Response (PR)] was calculated. VGPR (IMWG): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 h PR (IMWG): ≥50% reduction of serum M-protein and reduction in 24 h urinary M-protein by ≥90% or to <200mg per 24 h | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 36 weeks |
|
|
|
| Secondary | CR Rate Based on the (Bladé) Criteria | The proportion of subjects evaluated as CR was calculated. CR (Bladé) requires all of the followings:
| Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 36 weeks |
|
|
|
| Secondary | Response Rate (Based on the Bladé Criteria) | The proportion of subjects evaluated as response (CR + PR) was calculated. PR (Bladé) requires 1. or all of the others:
| Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 36 weeks |
|
|
|
| Secondary | Response Rate (Based on the Modified SWOG Criteria) | The proportion of subjects evaluated as response (CR + PR) was calculated. PR (SWOG) requires the followings:
| Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 36 weeks |
|
|
|
| Secondary | Progression-Free Survival (PFS) | PFS is the period from patient registration to either the date of recurrence, exacerbation, progression or death. Recurrence, exacerbation, progression were assessed from serum M-protein, urine M-protein, serum free light chain (FLC), the percentage of marrow plasma cells, disappearance of clonal plasma cells, plasma cell tumor in soft tissue, and bone lesion. | Posted | Median | Full Range | Days | Up to 2 years |
|
|
|
| Secondary | Time to Treatment Failure (TTF) | TTF is the period from patient registration to either the date of recurrence, exacerbation, progression, death or discontinuation of treatment. | Posted | Median | Full Range | Days | Up to 2 years |
|
|
|
| Secondary | Duration of Response (DOR) | DOR is the period from the date of achieving CR or PR to either the date of recurrence, exacerbation, progression or death. | Posted | Median | Full Range | Days | Up to 2 years |
|
|
|
| Secondary | Overall Survival (OS) | OS is the period from the date of patient registration to the date of death. | Posted | Median | Full Range | Days | Up to 2 years |
|
|
|
| Secondary | Number of Subjects With Adverse Event, Related Adverse Event, Serious Adverse Event, and Related Serious Adverse Event | Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.02, Japan Clinical Oncology Group/Japan Society of Clinical Oncology (JCOG/JSCO) version, and were encoded using Medical Dictionary for Regulatory Activities (MedDRA). | Posted | Number | Participants | Up to 2 years |
|
|
|
| Secondary | Number of Adverse Events, Related Adverse Events, Serious Adverse Events, and Related Serious Adverse Events | Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.02, Japan Clinical Oncology Group/Japan Society of Clinical Oncology (JCOG/JSCO) version, and were encoded using Medical Dictionary for Regulatory Activities (MedDRA). | Posted | Number | Events | Up to 2 years |
|
|
|
| Secondary | Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values | Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using 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 AE | Posted | Number | Participants | Up to 2 years |
|
|
|
| Secondary | Number of Abnormalities (Grade ≥3) in Laboratory Test Values | Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using CTCAE. | Posted | Number | Events | Up to 2 years |
|
|
|
| Secondary | Pharmacokinetic Parameters (Cmax) | Plasma pharmacokinetics (Cmax) of unchanged bendamustine | Posted | Mean | Standard Deviation | ng/mL | On Day 1 only |
|
|
|
| Secondary | Pharmacokinetic Parameters (Tmax) | Plasma pharmacokinetics (tmax) of unchanged bendamustine | Posted | Mean | Standard Deviation | h | On Day 1 only |
|
|
|
| Secondary | Pharmacokinetic Parameters (AUC) | Plasma pharmacokinetics (AUC) of unchanged bendamustine | Posted | Mean | Standard Deviation | ng・h/mL | On Day 1 only |
|
|
|
| Secondary | Pharmacokinetic Parameters (t1/2) | Plasma pharmacokinetics (t1/2) of unchanged bendamustine | Posted | Mean | Standard Deviation | h | On Day 1 only |
|
|
|
| 2 |
| 5 |
| 5 |
| 5 |
| Septic shock | Infections and infestations | MedDRA (14.1) |
|
| Pneumonia bacterial | Infections and infestations | MedDRA (14.1) |
|
| Acute respiratory distress syndrome | Infections and infestations | MedDRA (14.1) |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (14.1) |
|
| Constipation | Gastrointestinal disorders | MedDRA (14.1) |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.1) |
|
| Nausea | Gastrointestinal disorders | MedDRA (14.1) |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (14.1) |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (14.1) |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.1) |
|
| Malaise | General disorders | MedDRA (14.1) |
|
| Oedema | General disorders | MedDRA (14.1) |
|
| Oedema peripheral | General disorders | MedDRA (14.1) |
|
| Pyrexia | General disorders | MedDRA (14.1) |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (14.1) |
|
| Infection | Infections and infestations | MedDRA (14.1) |
|
| Pharyngitis | Infections and infestations | MedDRA (14.1) |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.1) |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (14.1) |
|
| Alanine aminotransferase increased | Investigations | MedDRA (14.1) |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (14.1) |
|
| Blood albumin decreased | Investigations | MedDRA (14.1) |
|
| Blood creatinine increased | Investigations | MedDRA (14.1) |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (14.1) |
|
| Blood potassium increased | Investigations | MedDRA (14.1) |
|
| Blood sodium decreased | Investigations | MedDRA (14.1) |
|
| Blood urea increased | Investigations | MedDRA (14.1) |
|
| Blood uric acid decreased | Investigations | MedDRA (14.1) |
|
| Blood uric acid increased | Investigations | MedDRA (14.1) |
|
| C-reactive protein increased | Investigations | MedDRA (14.1) |
|
| CD4 lymphocytes decreased | Investigations | MedDRA (14.1) |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (14.1) |
|
| Haemoglobin decreased | Investigations | MedDRA (14.1) |
|
| Lymphocyte count decreased | Investigations | MedDRA (14.1) |
|
| Neutrophil count decreased | Investigations | MedDRA (14.1) |
|
| Neutrophil count increased | Investigations | MedDRA (14.1) |
|
| Platelet count decreased | Investigations | MedDRA (14.1) |
|
| Protein total decreased | Investigations | MedDRA (14.1) |
|
| Weight increased | Investigations | MedDRA (14.1) |
|
| White blood cell count decreased | Investigations | MedDRA (14.1) |
|
| White blood cell count increased | Investigations | MedDRA (14.1) |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (14.1) |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (14.1) |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.1) |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (14.1) |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.1) |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (14.1) |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (14.1) |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.1) |
|
| Scab | Skin and subcutaneous tissue disorders | MedDRA (14.1) |
|
| Toxic skin eruption | Skin and subcutaneous tissue disorders | MedDRA (14.1) |
|
| Circulatory collapse | Vascular disorders | MedDRA (14.1) |
|
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|---|
|
| Subjects with related serious adverse event |
|
| Title | Measurements |
|---|---|
|
| Related serious adverse events |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|