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Phase I/II Study of SyB L-0501RI in Combination With Rituximab to Treat Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03900377
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
SymBio Pharmaceuticals

Brief Summary:
For SyB L-0501RI administered by an intravenous rapid infusion in combination with rituximab, the safety will be investigated in previously untreated patients with low-grade B-cell non-Hodgkin's lymphoma (Lg-B-NHL) or mantle cell lymphoma (MCL), and the safety and tolerability will be investigated in patients with recurrent/refractory diffuse large B-cell lymphoma (DLBCL).

Condition or disease Intervention/treatment Phase
Lymphoma, B-cell, Diffuse Drug: SyB L-0501RI Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Phase I/II Study to Investigate the Safety and Tolerability of SyB L-0501RI (Bendamustine Hydrochloride for Injection) Administered As an Intravenous (IV) Rapid Infusion Over 10 Minutes
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: Lg-B-NHL or MCL
For previously untreated patients with Lg-B-NHL or MCL, rituximab will be intravenously administered at 375 mg/m^2 on Day 0 (the day before Day 1 only in Cycle 1), and SyB L-0501RI will be intravenously administered at 90 mg/m^2/day on Day 1 and Day 2 of each 28-day cycle with up to 6 cycles.
Drug: SyB L-0501RI
The specified dose of SyB L-0501RI and rituximab will be administered by intravenous rapid infusion over 10 minutes on specified days.
Other Name: Rituximab

Experimental: DLBCL
For patients with recurrent or refractory DLBCL, rituximab will be intravenously administered at 375 mg/m^2 on Day 1, and SyB L-0501RI will be intravenously administered at 120 mg/m^2/day on Day 2 and Day 3 of each 21-day cycle with up to 6 cycles.
Drug: SyB L-0501RI
The specified dose of SyB L-0501RI and rituximab will be administered by intravenous rapid infusion over 10 minutes on specified days.
Other Name: Rituximab




Primary Outcome Measures :
  1. Adverse events (type, frequency, severity) [ Time Frame: Up to 36 weeks ]
  2. Number of subjects with adverse event [ Time Frame: Up to 36 weeks ]
  3. Number of adverse events [ Time Frame: Up to 36 weeks ]
  4. Number of subjects with abnormality (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥3) in laboratory test values [ Time Frame: Up to 36 weeks ]
  5. Number of subjects with grade ≥3 physical examination finding [ Time Frame: Up to 36 weeks ]
  6. Number of subjects with dose limiting toxicity in DLBCL arm [ Time Frame: Up to 36 weeks ]

Secondary Outcome Measures :
  1. Complete response (CR) rate [ Time Frame: Up to 36 weeks ]
  2. Overall response rate (antitumor effect : ≥ partial response [PR]) [ Time Frame: Up to 36 weeks ]
  3. Progression-free survival (PFS) [ Time Frame: Up to 36 weeks ]
  4. The maximum concentration (Cmax) of unchanged SyB L-0501 [ Time Frame: Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) ]
  5. The maximum drug concentration time (Tmax) of unchanged SyB L-0501 [ Time Frame: Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) ]
  6. The area under the curve (AUC) for unchanged SyB L-0501 [ Time Frame: Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) ]
  7. The half-life period (T1/2) of unchanged SyB L-0501 [ Time Frame: Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

For previously untreated patients with Lg-B-NHL or MCL

Inclusion Criteria

Patients who satisfy all of the conditions listed below:

▪ Patients who satisfy all of the following criteria A) to D): A) Patients who are histopathologically confirmed to have one of the following subtypes of CD20 (cluster of differentiation 20)-positive Lg-B-NHL or MCL (excluding transformed lymphoma) by lymph node biopsy or evaluable tissue biopsy (World Health Organization [WHO] histological classification [4th edition]).

  • Small lymphocytic lymphoma
  • Splenic marginal zone lymphoma
  • Lymphoplasmacytic lymphoma
  • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)
  • Nodal marginal zone lymphoma
  • Follicular lymphoma (Grade 1, 2, 3a)
  • MCL B) Patients who have at least one measurable lesion (>1.5 cm in major axis on computed tomography [CT]).

C) Patients without a history of treatment for lymphoma. D) Patients with at least one of the following clinical signs or symptoms (with the exception of MCL patients).

  1. Bulky disease >7 cm in major axis on CT (excluding lesions in the spleen)
  2. B symptoms

    • Unexplained fever exceeding 38.0ºC
    • Night sweats
    • Weight loss of more than 10% within 6 months before registration
  3. Elevated serum lactate dehydrogenase (LDH) or β2-microglobulin level
  4. Involvement of at least 3 regional lymph nodes >3 cm in major axis on CT
  5. Symptomatic splenomegaly
  6. Compressive symptoms
  7. Pleural effusion and/or ascites

    • Patients aged between 20 and 79 years (at the time of registration).
    • Patients who are expected to survive for at least 3 months.
    • Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
    • Patients with adequate functional reserve of major organs (bone marrow, heart, lungs, liver, kidneys, etc.).

      • Neutrophil count: ≥1,500/mm^3
      • Platelet count: ≥75,000/mm^3
      • Aspartate aminotransferase (AST) [glutamic oxaloacetic transaminase [GOT]): ≤3.0 times the institution's upper limit of normal (ULN)
      • Alanine aminotransferase (ALT) [glutamic pyruvic transaminase (GPT)]: ≤3.0 times the institution's ULN
      • Total bilirubin: <2.0 mg/dL
      • Serum creatinine: <2.0 mg/dL
      • Percutaneous arterial oxygen saturation (SpO2): ≥95% or Partial arterial oxygen pressure (PaO2): ≥65 mmHg
      • No abnormal findings requiring treatment on electrocardiogram (ECG)
      • Left ventricular ejection fraction (LVEF) on echocardiography: ≥55%
    • Patients who have provided written informed consent to participate in this study.

Exclusion Criteria

Patients who meet any of the following conditions will be excluded:

  • MCL patients aged ≤65 years (at the time of registration).
  • Patients who have a history of treatment for Lg-B-NHL or MCL (chemotherapy, radiotherapy, antibody therapy or antitumor steroid therapy).
  • Patients who have previously received hematopoietic stem cell transplantation.
  • Patients with invasion to central nervous system (CNS) or clinical symptoms suspected of CNS invasion.
  • Patients with serious active infection (requiring antibiotic, antifungal, or antiviral IV injection).
  • Patients with serious complications (such as hepatic failure and renal failure).
  • Patients with concurrent or previous, serious cardiac disease (e.g., myocardial infarction, ischemic heart disease); however, patients with arrhythmias are allowed to be enrolled if it does not require treatment at the time of registration.
  • Patients with serious gastrointestinal symptoms (such as high-grade or severe nausea/vomiting or diarrhea).
  • Patients with malignant pleural effusion, pericardial effusion, or ascites.
  • Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody (patients with positive hepatitis B virus [HBV]-DNA quantitative test results if they are negative for HBs antigen and positive for HBs antibody or hepatitis B core [HBc] antibody).
  • Patients with serious bleeding tendencies (such as disseminated intravascular coagulation [DIC]).
  • Patients with a fever of 38.0ºC or higher (with the exception of fever developing as a B symptom).
  • Patients with concurrent or previous interstitial pneumonia, pulmonary fibrosis, or chronic obstructive pulmonary disease.
  • Patients with active multiple primary cancers or patients with a history of other malignancy within the past 5 years, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or digestive organs.
  • Patients with concurrent or previous autoimmune hemolytic anemia.
  • Patients who have previously received bendamustine hydrochloride.
  • Patients who have received a cytokine preparation, such as granulocyte colony- stimulating factor (G-CSF) or erythropoietin, or blood transfusions within 2 weeks before a screening test for this study.
  • Patients who have received other investigational products or unapproved drugs within 3 months before registration for this study.
  • Patients with a history of allergy to medications similar to SyB L-0501RI (e.g., alkylating agents and purine-nucleoside derivatives).
  • Patients who cannot tolerate rituximab.
  • Pregnant, possibly pregnant, or lactating women.
  • Patients, whether male or female, who do not agree to use contraception.

Duration:

Male patients; during the treatment period and for 6 months after treatment Female patients with no menstruation; during the treatment period Female patients with menstruation; during the treatment period and for 3 months after treatment

  • Patients with drug addiction, narcotic addiction, or alcohol dependence.
  • Patients who are unable to take pre-treatment medication due to drug allergies or the like.
  • Patients who are otherwise judged by the investigator or subinvestigator to be unsuitable as a subject.

For patients with recurrent or refractory DLBCL

Inclusion Criteria

Patients who satisfy all of the conditions listed below:

▪ Patients who satisfy both of the following criteria A and B: A) Patients who are histopathologically confirmed to have CD20-positive DLBCL (excluding transformed lymphoma) by lymph node biopsy or evaluable tissue biopsy (WHO histological classification [4th edition]).

B) Patients with recurrent or refractory DLBCL who have had disease progression after standard rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy or R-CHOP-like therapy as first-line treatment.

  • Patients aged between 20 and 79 years (at the time of registration).
  • Patients who are expected to survive for at least 3 months.
  • Patients with an ECOG PS of 0 to 2.
  • Patients with adequate functional reserve of major organs (bone marrow, heart, lungs, liver, kidneys, etc.).

    • Neutrophil count: ≥1,500/mm^3
    • Platelet count: ≥75,000/mm^3
    • AST (GOT): ≤3.0 times the institution's ULN
    • ALT (GPT): ≤3.0 times the institution's ULN
    • Total bilirubin: <2.0 mg/dL
    • Serum creatinine: <2.0 mg/dL
    • SpO2: ≥95% or PaO2: ≥65 mmHg
    • No abnormal findings requiring treatment on ECG
    • LVEF on echocardiography: ≥55%
  • Patients who have provided written informed consent to participate in this study.

Exclusion Criteria

Patients who meet any of the following conditions will be excluded:

  • Patients with an off-treatment interval of less than 3 weeks between the last day of preceding treatment (chemotherapy, radiotherapy, antibody therapy, or antitumor steroid therapy) for DLBCL and the day of registration for this study.
  • Patients who are judged by the investigator or subinvestigator to be suitable for autologous peripheral blood stem cell transplantation.
  • Patients who have previously received allogeneic hematopoietic stem cell transplantation.
  • Patients who have previously received radioimmunotherapy
  • Patients with invasion to CNS or clinical symptoms suspected of CNS invasion.
  • Patients with serious active infection (requiring antibiotic, antifungal, or antiviral IV injection).
  • Patients with serious complications (such as hepatic failure and renal failure).
  • Patients with concurrent or previous, serious cardiac disease (e.g., myocardial infarction, ischemic heart disease); however, patients with arrhythmias are allowed to be enrolled if it does not require treatment at the time of registration.
  • Patients with serious gastrointestinal symptoms (such as high-grade or severe nausea/vomiting or diarrhea).
  • Patients with malignant pleural effusion, pericardial effusion, or ascites.
  • Patients positive for HBs antigen, HCV antibody, or HIV antibody (patients with positive HBV-DNA quantitative test results if they are negative for HBs antigen and positive for HBs antibody or HBc antibody).
  • Patients with serious bleeding tendencies (such as DIC).
  • Patients with a fever of 38.0ºC or higher (with the exception of fever developing as a B symptom).
  • Patients with concurrent or previous interstitial pneumonia, pulmonary fibrosis, or chronic obstructive pulmonary disease.
  • Patients with active multiple primary cancers or patients with a history of other malignancy within the past 5 years, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or digestive organs.
  • Patients with concurrent or previous autoimmune hemolytic anemia.
  • Patients who have previously received bendamustine hydrochloride.
  • Patients who have received a cytokine preparation, such as G-CSF or erythropoietin, or blood transfusions within 2 weeks before a screening test for this study.
  • Patients who have received other investigational products or unapproved drugs within 3 months before registration for this study.
  • Patients with a history of allergy to medications similar to SyB L-0501RI (e.g., alkylating agents and purine-nucleoside derivatives).
  • Patients who cannot tolerate rituximab.
  • Pregnant, possibly pregnant, or lactating women.
  • Patients, whether male or female, who do not agree to use contraception.

Duration:

Male patients; during the treatment period and for 6 months after treatment Female patients with no menstruation; during the treatment period Female patients with menstruation; during the treatment period and for 3 months after treatment

  • Patients with drug addiction, narcotic addiction, or alcohol dependence.
  • Patients who are unable to take pre-treatment medication due to drug allergies or the like.
  • Patients who are otherwise judged by the investigator or subinvestigator to be unsuitable as a subject.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03900377


Contacts
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Contact: Katsuhisa Goto +81-3-5472-1127 kgoto.34@symbiopharma.com
Contact: Naoko Takahashi +81-3-5472-1127 ntakahashi.nt03@symbiopharma.com

Locations
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Japan
Research Site Recruiting
Nagoya, Aichi, Japan
Research Site Recruiting
Ōta, Gunma, Japan
Research Site Recruiting
Sapporo, Hokkaido, Japan
Research Site Recruiting
Kobe, Hyogo, Japan
Research Site Recruiting
Isehara, Kanagawa, Japan
Research Site Recruiting
Kurashiki, Okayama, Japan
Research Site Recruiting
Koto-ku, Tokyo, Japan
Research Site Recruiting
Akita, Japan
Research Site Recruiting
Fukuoka, Japan
Research Site Recruiting
Kagoshima, Japan
Research Site Recruiting
Kumamoto, Japan
Research Site Recruiting
Kyoto, Japan
Research Site Recruiting
Okayama, Japan
Research Site Recruiting
Yamagata, Japan
Sponsors and Collaborators
SymBio Pharmaceuticals
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Responsible Party: SymBio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03900377    
Other Study ID Numbers: 2018001
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SymBio Pharmaceuticals:
Lymphoma, B-cell, Diffuse, SyB L-0501RI
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents