Efficacy and Safety Study of SyB L-0501 for Patients With Multiple Myeloma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
SymBio Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01179490
First received: August 2, 2010
Last updated: March 15, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: SyB L-0501
Drug: prednisolone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Phase 2 Study of SyB L-0501 (Bendamustine Hydrochloride) for Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by SymBio Pharmaceuticals:

Primary Outcome Measures:
  • Complete Response (CR) Rate [Based on the Modified Southwest Oncology Group (SWOG) Criteria] [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    The proportion of subjects evaluated as CR was calculated.

    CR (modified SWOG) requires all of the followings:

    1. Decline in serum myeloma protein by ≥75% to ≤25 g/L
    2. Reduction in 24 h urinary protein by ≥90% to ≤200 mg/24 h
    3. No increase in skeletal destruction
    4. Serum calcium within normal range
    5. No blood transfusion required in the previous 3 months


Secondary Outcome Measures:
  • CR Rate [Based on the International Myeloma Working Group (IMWG) Criteria] [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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


  • Response Rate (Based on the IMWG Criteria) [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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


  • CR Rate Based on the (Bladé) Criteria [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    The proportion of subjects evaluated as CR was calculated.

    CR (Bladé) requires all of the followings:

    1. Absence of the original monoclonal paraprotein in serum and urine by immunofixation, maintained for a minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR.
    2. <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed. If absence of monoclonal protein is sustained for 6 weeks it is not necessary to repeat the bone marrow, except in patients with non-secretory myeloma where the marrow examination must be repeated after an interval of at least 6 weeks to confirm CR.
    3. No increase in size or number of lytic bone lesions (development of a compression fracture does not exclude response)
    4. Disappearance of soft tissue plasmacytomas

  • Response Rate (Based on the Bladé Criteria) [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    The proportion of subjects evaluated as response (CR + PR) was calculated.

    PR (Bladé) requires 1. or all of the others:

    1. Some, but not all, of the criteria for CR are fulfilled
    2. ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks.
    3. Reduction in 24 h urinary light chain excretion either by ≥90% or to <200 mg, maintained for a minimum of 6 weeks.
    4. For patients with non-secretory myeloma only, ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks.
    5. ≥50% reduction in the size of soft tissue plasmacytomas (by radiography or clinical examination).
    6. No increase in size or number of lytic bone lesions (development of a compression fracture does not exclude response).

  • Response Rate (Based on the Modified SWOG Criteria) [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    The proportion of subjects evaluated as response (CR + PR) was calculated.

    PR (SWOG) requires the followings:

    1. Decline in myeloma protein of ≥25%-<74% in serum myeloma protein
    2. Reduction in 24h urinary myeloma protein of ≥25%-<89%
    3. No increase in skeletal destruction
    4. Serum calcium within normal range

  • Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

    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.


  • Time to Treatment Failure (TTF) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    TTF is the period from patient registration to either the date of recurrence, exacerbation, progression, death or discontinuation of treatment.

  • Duration of Response (DOR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    DOR is the period from the date of achieving CR or PR to either the date of recurrence, exacerbation, progression or death.

  • Overall Survival (OS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    OS is the period from the date of patient registration to the date of death.

  • Number of Subjects With Adverse Event, Related Adverse Event, Serious Adverse Event, and Related Serious Adverse Event [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    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).

  • Number of Adverse Events, Related Adverse Events, Serious Adverse Events, and Related Serious Adverse Events [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    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).

  • Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

    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


  • Number of Abnormalities (Grade ≥3) in Laboratory Test Values [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using CTCAE.

  • Pharmacokinetic Parameters (Cmax) [ Time Frame: On Day 1 only ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics (Cmax) of unchanged bendamustine

  • Pharmacokinetic Parameters (Tmax) [ Time Frame: On Day 1 only ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics (tmax) of unchanged bendamustine

  • Pharmacokinetic Parameters (AUC) [ Time Frame: On Day 1 only ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics (AUC) of unchanged bendamustine

  • Pharmacokinetic Parameters (t1/2) [ Time Frame: On Day 1 only ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics (t1/2) of unchanged bendamustine


Enrollment: 5
Study Start Date: September 2010
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: SyB L-0501
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).
Drug: prednisolone
Prednisolone will be administered (60 mg/m2/day) orally for 4 consecutive days and the course will be observed for the next 24 days.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  • Patients with measurable lesions
  • Patients with no history of treatment (no history of chemotherapy or radiotherapy)
  • Patients should not be considered candidates for high dose therapy/autologous stem cell transplantation due to coexistent medical conditions, advanced age, poor performance status, refusal of high dose chemotherapy, or other reasons as judged by the patient and/or physician.
  • Expected survival of at least 3 months
  • Patients aged between 20 and 79 years (at the time of provisional registration)
  • Performance status (P.S.) grade 0-2. P.S. 3 possible only for osteolytic lesions
  • Patients with adequately maintained organ function (e.g., bone marrow, heart, lungs, liver, kidneys,)
  • Patients from whom written consent to participate in this study has been obtained.

Exclusion Criteria:

Patients are excluded from participating in the study if 1 or more of the following criteria are met:

  • Patients with apparent infections (including viral infections)
  • Patients with serious complications (hepatic failure, renal failure, or diabetes with insulin administration)
  • Patients with complications or a medical history of serious cardiac disease (e.g., myocardial infarction, ischemic heart disease) within 2 years before preliminary registration. Patients with arrhythmia requiring treatment.
  • Patients with serious gastrointestinal symptoms (profound or serious nausea / vomiting or diarrhea, etc.)
  • Patients who were hepatitis B virus antigen (HBsAG)-positive, hepatitis C virus (HCV) antibody-positive or human immunodeficiency virus (HIV) antibody-positive
  • Patients with a serious bleeding tendency [e.g., Disseminated intravascular coagulation (DIC)]
  • Patients with interstitial pneumonia, pulmonary fibrosis or pulmonary emphysema requiring treatment, or such diseases in the past
  • Patients with apparent amyloidosis as a complication
  • Patients with clinical symptoms of invasion or suspected invasion of the central nervous system.
  • Patients with active multiple cancers
  • Patients who have or previously had autoimmune hemolytic anemia.
  • Patients administered this investigational drug in the past
  • Patients who received hematopoietic stem cell transplantation in the past.
  • Patients who received cytokines such as granulocyte colony stimulating factor (G-CSF) or erythropoietin or a blood transfusion within 1 week before the screening examination prior to preliminary registration for this study
  • Patients who were administered an investigational drug during a clinical study or an unapproved drug within 3 months prior to preliminary registration in this study
  • Patients with prior allergies to medications similar to the investigational drug (e.g., alkylating agents, or purine nucleotide analogs), mannitol or prednisolone
  • Patients with drug addiction, narcotic addiction or alcoholism.
  • Patients who were pregnant, breastfeeding women or who had a possibility to be pregnant
  • Patients who do not agree to contraception during the following periods. For males, during or for 6 months after completion of administration of the investigational drug. For females, during or for 3 months after completion of administration of the investigational drug
  • Patients whom the investigator or the sub-investigators considered to be inappropriate for the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01179490

Locations
Japan
Research site
Nagoya, Aichi, Japan
Research site
Isehara, Kanagawa, Japan
Research site
Fukuoka, Japan
Sponsors and Collaborators
SymBio Pharmaceuticals
Investigators
Study Chair: Shinsuke Iida, MD, Ph D Nagoya City University Graduate School of Medical Sciences
  More Information

No publications provided

Responsible Party: SymBio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01179490     History of Changes
Other Study ID Numbers: 2010002
Study First Received: August 2, 2010
Results First Received: December 2, 2012
Last Updated: March 15, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by SymBio Pharmaceuticals:
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on October 23, 2014