Study of SyB L-0501 to Treat Relapsed/Refractory Multiple Myeloma
Condition: Relapsed/Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: SyB L-0501
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 20 Years
Maximum age: 79 Years

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.
    

Eligibility criteria:

        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)

          2. 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

          3. 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

          4. 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).

          5. Patients who are expected to survive for at least 3 months

          6. Patients aged from 20 to 79 years at the time of interim registration

          7. Performance Status (P.S.) of 0 to 125. However, P.S. 2 due to pain from lytic bone
             lesions is acceptable

          8. 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%

          9. 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

         20. Patients otherwise judged by the investigator or sub-investigator to be unsuitable for
             inclusion in this study