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Lymphoma, B-cell, DiffusePhase 1/2NCT03900377

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

A Phase 1/2 study testing SyB L-0501RI in people with Lymphoma, B-cell, Diffuse, run by SymBio Pharmaceuticals at 14 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 20 to 79 years
Conditions the study is for
Lymphoma, B-cell, Diffuse
What is being tested?
SyB L-0501RI
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
14 sitesJapan
Study dates
1 Apr 2019to 26 Feb 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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]).
  • 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).
  • Bulky disease >7 cm in major axis on CT (excluding lesions in the spleen)
  • B symptoms
  • Unexplained fever exceeding 38.0ºC
  • Night sweats
  • Weight loss of more than 10% within 6 months before registration
  • Elevated serum lactate dehydrogenase (LDH) or β2-microglobulin level
  • Involvement of at least 3 regional lymph nodes >3 cm in major axis on CT
  • Symptomatic splenomegaly
  • Compressive symptoms
  • 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.
  • 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]).
  • 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.

Who cannot join

  • 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).
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  • 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
  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Japan14 sites

  • Research Site

    Akita

  • Research Site

    Fukuoka

  • Research Site

    Isehara, Kanagawa

  • Research Site

    Kagoshima

  • Research Site

    Kobe, Hyōgo

  • Research Site

    Koto-ku, Tokyo

  • Research Site

    Kumamoto

  • Research Site

    Kurashiki, Okayama-ken

  • Research Site

    Kyoto

  • Research Site

    Nagoya, Aichi-ken

  • Research Site

    Okayama

  • Research Site

    Ōta, Gunma

  • Research Site

    Sapporo, Hokkaido

  • Research Site

    Yamagata

Other trials in Japan

About this study

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

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).

Being tested
SyB L-0501RI
Keywords
Lymphoma, B-cell, Diffuse, SyB L-0501RI
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SyB L-0501RIDrug

    Also called Rituximab

    The specified dose of SyB L-0501RI and rituximab will be administered by intravenous rapid infusion over 10 minutes on specified days.

Study groups in NCT03900377
Study groupRoleWhat they receive
Lg-B-NHL or MCLExperimentalFor 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.
Receives: Drug: SyB L-0501RI
DLBCLExperimentalFor 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.
Receives: Drug: SyB L-0501RI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events (type, frequency, severity)

    Measured: Up to 36 weeks

  2. Number of subjects with adverse event

    Measured: Up to 36 weeks

  3. Number of adverse events

    Measured: Up to 36 weeks

  4. Number of subjects with abnormality (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥3) in laboratory test values

    Measured: Up to 36 weeks

  5. Number of subjects with grade ≥3 physical examination finding

    Measured: Up to 36 weeks

  6. Number of subjects with dose limiting toxicity in DLBCL arm

    Measured: Up to 36 weeks

Secondary outcomes (7)

  1. Complete response (CR) rate

    Measured: Up to 36 weeks

  2. Overall response rate (antitumor effect : ≥ partial response [PR])

    Measured: Up to 36 weeks

  3. Progression-free survival (PFS)

    Measured: Up to 36 weeks

  4. The maximum concentration (Cmax) of unchanged SyB L-0501

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2019
  2. Study start1 Apr 2019
  3. Primary completion9 Sep 2020
  4. Study completion26 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03900377
Sponsor's protocol ID
2018001
Status last verified
Jun 2023
First submitted
6 Mar 2019
Last updated
24 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ishizawa K, Yokoyama M, Kato H, Yamamoto K, Makita M, Ando K, Ueda Y, Tachikawa Y, Suehiro Y, Kurosawa M, Kameoka Y, Nagai H, Uoshima N, Ishikawa T, Hidaka M, Ito Y, Utsunomiya A, Fukushima K, Ogura M. A phase I/II study of 10-min dosing of bendamustine hydrochloride (rapid infusion formulation) in patients with previously untreated indolent B-cell non-Hodgkin lymphoma, mantle cell lymphoma, or relapsed/refractory diffuse large B-cell lymphoma in Japan. Cancer Chemother Pharmacol. 2022 Jul;90(1):83-95. doi: 10.1007/s00280-022-04442-2. Epub 2022 Jul 7.

    PubMed 35796785

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SyB L-0501RI in people with Lymphoma, B-cell, Diffuse, run by SymBio Pharmaceuticals at 14 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 58 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (type, frequency, severity) (time frame: Up to 36 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03900377, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023; AzTrials last refreshed its copy on 7 Nov 2026.

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