Relapsed or Refractory Non-Hodgkin's LymphomaPhase 1NCT06082596
Study of BEBT-908 in Subjects With Advanced Hematological Tumors
A Phase 1 study testing BEBT-908 for injection in people with Relapsed or Refractory Non-Hodgkin's Lymphoma and Relapsed or Refractory Multiple Myeloma, run by BeBetter Med Inc at 1 site in China.
Trial summary
The purpose of this study was to evaluate the safety and tolerance of BEBT-908 for injection in the treatment of recurrent refractory malignant lymphoma, multiple myeloma and chronic lymphoblastic leukemia, and to obtain the pharmacokinetic data and preliminary efficacy of BEBT-908 for injection, and to explore the… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Relapsed or Refractory Non-Hodgkin's Lymphoma, Relapsed or Refractory Multiple Myeloma
- What is being tested?
- BEBT-908 for injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2016to 8 Mar 2019
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dose escalation phase:
- Age ≥ 18 and ≤ 70 years old, both men and women.
- Tissue biopsy, bone marrow examination and / or hematological examination confirmed relapsed refractory （Note 1） malignant lymphoma, chronic lymphoblastic leukemia and multiple myeloma. （Note 2 and Note 3）
- With measurable lesions . (Note 4)
- Eastern Cooperative Oncology Group (ECOG) score≤2.
- The level of organ function must meet the following requirements:
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- Bone marrow:
- Absolute neutrophil count (ANC) ≥ 1000 /μL (if recent bone marrow biopsies or smears prove tumor progression, this index can be < 1000/μL).
- Hemoglobin (HGB) ≥ 9g/dL.
- Platelet count (PLT) ≥ 1000000/μL (if recent bone marrow biopsies or smears prove tumor progression, this index can be < 1000000/μL).
- Liver function:
- In patients with serum bilirubin ≤ 1.5 ×upper limit of normal value (ULN) or Gilbert syndrome, the total bilirubin is less than 3.0 × ULN and direct bilirubin is within the normal range.
- Serum creatinine < 1.5×ULN; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST)or Alkaline phosphatase (ALP) ≤ 2.5 ×ULN.
- When there is liver metastasis, ALT, AST or ALP ≤ 5 × ULN.
- 6.Non-pregnant women and male and female subjects who did not consider fertility during and after the trial, or who had preserved sperm or eggs in vitro before the trial, or reconsidered fertility according to reproductive function 5 years after the end of the trial.
- 7.After a comprehensive understanding, the subjects were willing to sign the informed consent form.
- Note 1: relapse or refractory is defined as follows:
- Chronic Lymphoblastic Leukemia: subjects who are ineffective after at least 2 chemotherapy regimens, and the subjects are not suitable or refuse to transplant. Relapse: the patient reached Complete Response (CR) or Partial Response (PR), and Progressive Disease (PD) ≥ 6 months later. Refractory: failed treatment (without CR or PR) or PD less than 6 months after the last chemotherapy.
- Malignant Lymphoma: refractory or relapse after at least 2 chemotherapy regimens.
- Multiple Myeloma: relapse or refractory is defined as relapse or disease progression after at least 2 chemotherapy regimens (refractory occurred during the last chemotherapy or within 60 days after the last medication).
- Note 2: Malignant Lymphoma includes B-cell non-Hodgkin's lymphoma, B-cell Hodgkin's lymphoma, diffuse large B-cell lymphoma, T-cell lymphoma and so on.
- Note 3: If the subjects can provide test results to confirm the nature of the disease and the researchers determine that the nature of the disease has not changed, there is no need for reexamination.
- Note 4: For subjects with malignant lymphoma, the lesions are measured by computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography (PET) / PET-CT. Bone marrow biopsy or smear may be performed in the evaluation of curative effect.
- For subjects with multiple myeloma, it can be accepted that bone marrow biopsy or smear may be performed during the evaluation of the curative effect.
- For subjects with chronic lymphoblastic leukemia, it can be accepted that bone marrow biopsy or smear may be performed during the evaluation of the curative effect.
- Dose expansion phase:
- After a comprehensive understanding, the subjects were willing to sign the informed consent form.
- Age ≥ 18 and ≤ 70 years old, both men and women.
- Tissue biopsy confirmed as relapse or refractory (Note 1) non-Hodgkin's lymphoma.
- With measurable lesions .(Note 4)
- Eastern Cooperative Oncology Group (ECOG) score≤2.
- The level of organ function must meet the following requirements:
- Bone marrow:
- Absolute neutrophil count (ANC) ≥ 1000 /μL.
- Hemoglobin (HGB) ≥ 8g/dL.
- Platelet count (PLT) ≥ 1000000/μL (if recent bone marrow biopsies or smears prove tumor progression, this index can be < 1000000/μL).
- Liver function:
- In patients with serum bilirubin ≤ 1.5 ×upper limit of normal value (ULN) or Gilbert syndrome, the total bilirubin is less than 3.0 × ULN and direct bilirubin is within the normal range.
- Serum creatinine < 1.5×ULN; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) or Alkaline phosphatase (ALP) ≤ 2.5 ×ULN.
- When there is liver metastasis, ALT, AST or ALP ≤ 5 × ULN.
- 7.Non-pregnant women and male and female subjects who did not consider fertility during and after the trial, or who had preserved sperm or eggs in vitro before the trial, or reconsidered fertility according to reproductive function 5 years after the end of the trial.
- Note 1: relapse or refractory is defined as refractory or relapse after at least 2 chemotherapy regimens.
- Note 2: The lesions are measured by computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography (PET) / PET-CT. Bone marrow biopsy or smear may be performed in the evaluation of curative effect.
Who cannot join
- Dose escalation phase:
- Severe allergies to research drugs or any of their excipients are known.
- Because the research drugs may have genotoxicity, mutagenicity and teratogenicity, the following subjects should be excluded: men and women who plan to reproduce within 5 years without in vitro preservation of sperm or eggs before the trial, unless follow-up studies confirm reproductive safety; pregnant or lactating women.
- The treatment of the subjects before the trial:
- Bone marrow transplantation was performed within 3 months before enrolling the group.
- Received bone marrow inhibitory chemotherapy or biotherapy within 3 weeks before enrolling the group.
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- Before enrolling the group, the subjects had been treated with any persistent or intermittent small molecular targeted drugs (Phosphoinositide 3-kinase (PI3K) inhibitors or Mammalian Target of Rapamycin (mTOR) inhibitors or Histone Deacetylase (HDAC) inhibitors). Subjects in the dose increasing phase of this study will not be subject to the exclusion criteria of this article if they participate in the expanded group phase screening.
- Within 3 months before enrolling the group, subjects received radiotherapy that affected the efficacy evaluation of this study, or local supportive radiotherapy that affected the bone marrow function of the subjects.
- Subjects received any hematopoietic colony stimulating factor therapy (such as granulocyte colony stimulating factor （G-CSF）, granulocyte macrophage colony stimulating factor（GM-CSF）) within 2 weeks before enrolling the group (Note 1).
- Major surgery was performed within 14 days before enrolling the group, or the side effects of the operation were not stable.
- Subjects received glucocorticoid prednisone daily >10mg (or equivalent drug) treatment within 7 days before enrollment. (Note 2)
- After the previous treatment (chemotherapy or biotherapy), there was persistent toxicity of grade 2 or above, which was not stable at the time of admission (except hair loss).
- The organ systems of the subjects were as follows:
- Diabetes mellitus with poorly controlled blood sugar.
- Severe lung disease (Common Terminology Criteria for Adverse Events Version 4.03（CTCAE V4.03）, III-IV).
- Active heart disease (Note 3) (New York Heart Association grade III and IV).
- Has significant renal or liver dysfunction.
- Poorly controlled active hepatitis B or C disease (Note 4).
- Primary central nervous system lymphoma or metastasis of central nervous system lymphoma.
- A history of mental illness or emotional disorder is judged by a researcher or psychiatrist (Note 5).
- Occurrence of disease transformation (such as Richter syndrome, prolymphocytic leukemia, etc.).
- Combined use of drugs that cause prolonged QT interval or twisted ventricular tachycardia.
- Clinical severe infection with active > CTCAE V4.03 Grade 2; human immunodeficiency virus (HIV) is known to be positive.
- Persistent diarrhea (duration ≥ 14 days).
- There are other active malignant tumors that may interfere with this study.
- Anything that significantly affects the parameters of pharmacokinetics.
- Currently receiving moderate and potent cytochrome P450 (CYP) 3A4 isozyme inhibitors or induction drugs (Note 6).
- Are participating in other clinical trials.
- Any condition that is unstable or may endanger the safety of subjects and their compliance with the study.
- The researchers believe that it is not suitable for subjects treated with this regimen.
- Note 1: subjects who began to receive erythropoietin or daipotene within 2 weeks before entering the group can be enrolled in the group.
- Note 2: if used to treat diseases other than lymphoma, such as rheumatoid arthritis, rheumatic polymyalgia, adrenocortical dysfunction or asthma, subjects can receive a maximum daily dose of 10mg with a stable dose of prednisone.
- Note 3: includes any of the following: left ventricular ejection fraction (LVEF) found by cardiac radionuclide scanning (Multigated Radionuclide Angiography (MUGA) ) or echocardiography (ECHO) < 45% Fridericia corrected QT (between QTcF ) > 450ms (QTcF formula); unstable angina pectoris; symptomatic pericarditis; abnormal recording of the left ventricular wall in areas with persistent elevated myocardial enzymes or persistent LVEF function measurements in the past 6 months of myocardial infarction. Has a history of congestive heart failure (New York College of Cardiology Cardiac function Classification III-IV), has a record of cardiomyopathy.
- Note 4: a detailed assessment of the history and risk factors of hepatitis B / C must be performed on all subjects during screening. In screening all subjects with positive medical history, quantitative detection of hepatitis B virus deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) was needed based on risk factors and previous confirmation of hepatitis B/C virus infection. Hepatitis B/C virus replication within the normal range can be included in this study.
- Note 5: including medical records of depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, suicidal attempts or suicidal ideation, or thoughts of "causing harm to others immediately", anxiety level 3 or above, etc.
- Note 6: allow a combination of inhibitors for weak CYP3A; a list of CYP3A4 inhibitors or inducers is shown in Annex 2 of the study scheme.
- Dose expansion phase:
- Severe allergies to research drugs or any of their excipients are known.
- Because the research drugs may have genotoxicity, mutagenicity and teratogenicity, the following subjects should be excluded: men and women who plan to reproduce within 5 years without in vitro preservation of sperm or eggs before the trial, unless follow-up studies confirm reproductive safety; pregnant or lactating women.
- The treatment of the subjects before the trial:
- Before enrolling the group, the subjects had been treated with any persistent or intermittent small molecular targeted drugs (Phosphoinositide 3-kinase (PI3K) inhibitors or Mammalian Target of Rapamycin (mTOR) inhibitors or Histone Deacetylase (HDAC) inhibitors). Subjects in the dose increasing phase of this study will not be subject to the exclusion criteria of this article if they participate in the expanded group phase screening.
- Subjects received any hematopoietic colony stimulating factor therapy (such as granulocyte colony stimulating factor （G-CSF）, granulocyte macrophage colony stimulating factor（GM-CSF）) within 2 weeks before enrolling the group (Note 1).
- Major surgery was performed within 14 days before enrolling the group, or the side effects of the operation were not stable.
- Subjects received glucocorticoid prednisone daily >10mg (or equivalent drug) treatment within 7 days before enrollment. (Note 2)
- After the previous treatment (chemotherapy or biotherapy), there was persistent toxicity of grade 2 or above, which was not stable at the time of admission (except hair loss).
- The organ systems of the subjects were as follows:
- Diabetes mellitus with poorly controlled blood sugar.
- Severe lung disease (Common Terminology Criteria for Adverse Events Version 4.03（CTCAE V4.03）, III-IV).
- Active heart disease (Note 3) (New York Heart Association grade III and IV).
- Has significant renal or liver dysfunction.
- Poorly controlled active hepatitis B or C disease (Note 4).
- Primary central nervous system lymphoma or metastasis of central nervous system lymphoma.
- A history of mental illness or emotional disorder is judged by a researcher or psychiatrist (Note 5).
- Occurrence of disease transformation (such as Richter syndrome, prolymphocytic leukemia, etc.).
- Combined use of drugs that cause prolonged QT interval or twisted ventricular tachycardia.
- Clinical severe infection with active > CTCAE V4.03 Grade 2; human immunodeficiency virus (HIV) is known to be positive.
- Persistent diarrhea (duration ≥14 days).
- There are other active malignant tumors that may interfere with this study.
- Anything that significantly affects the parameters of pharmacokinetics.
- Currently receiving moderate and potent cytochrome P450 (CYP) 3A4 isozyme inhibitors or induction drugs (Note 6).
- Are participating in other clinical trials.
- Any condition that is unstable or may endanger the safety of subjects and their compliance with the study.
- The researchers believe that it is not suitable for subjects treated with this regimen.
- Note 1: subjects who began to receive erythropoietin or daipotene within 2 weeks before entering the group can be enrolled in the group.
- Note 2: if used to treat diseases other than lymphoma, such as rheumatoid arthritis, rheumatic polymyalgia, adrenocortical dysfunction or asthma, subjects can receive a maximum daily dose of 10mg with a stable dose of prednisone.
- Note 3: includes any of the following: left ventricular ejection fraction (LVEF) found by cardiac radionuclide scanning (Multigated Radionuclide Angiography (MUGA) ) or echocardiography (ECHO) < 45% Fridericia corrected QT (between QTcF) > 450ms (QTcF formula); unstable angina pectoris; symptomatic pericarditis; abnormal recording of the left ventricular wall in areas with persistent elevated myocardial enzymes or persistent LVEF function measurements in the past 6 months of myocardial infarction. Has a history of congestive heart failure (New York College of Cardiology Cardiac function Classification III-IV), has a record of cardiomyopathy.
- Note 4: a detailed assessment of the history and risk factors of hepatitis B / C must be performed on all subjects during screening. In screening all subjects with positive medical history, quantitative detection of hepatitis B virus deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) was needed based on risk factors and previous confirmation of hepatitis B/C virus infection. Hepatitis B/C virus replication within the normal range can be included in this study.
- Note 5: including medical records of depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, suicidal attempts or suicidal ideation, or thoughts of "causing harm to others immediately", anxiety level 3 or above, etc.
- Note 6: allow a combination of inhibitors for weak CYP3A; a list of CYP3A4 inhibitors or inducers is shown in Annex 2 of the study scheme.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter, Open, Phase I Clinical Study of BEBT-908 for Injection in the Treatment of Relapsed Refractory Malignant Lymphoma, Multiple Myeloma and Chronic Lymphoblastic Leukemia
The purpose of this study was to evaluate the safety and tolerance of BEBT-908 for injection in the treatment of recurrent refractory malignant lymphoma, multiple myeloma and chronic lymphoblastic leukemia, and to obtain the pharmacokinetic data and preliminary efficacy of BEBT-908 for injection, and to explore the relationship between the safety and efficacy of BEBT-908 for injection and related biomarkers.
Read the detailed description
This study is divided into two stages: dose increasing stage and expanding into the group.
Dose escalation phase: The initial dose was 10mg/m2, and the subsequent dose group was increased by 100% until the first case of grade 2 non-blood toxicity or grade 3 hematological toxicity related to the test drug and no dose-limiting toxicity, then the dose was increased by 50%, and a total of 5 dose groups were designed. In this stage, all subjects received a single dose first and were observed for 6 days. After the end of the observation period, if the subjects were safely tolerant to a single dose，then will receive the same dose of treatment for a cycle, administration regimen is 3 times a week, continuous administration for 2 weeks, withdrawal for 1 week, a total of 21 days as a cycle.
Dose expansion phase: according to the results of pharmacokinetics, safety and efficacy of BEBT-908 for injection obtained in the dose escalation phase, we plan to select two doses to further observe the safety, pharmacokinetic characteristics and preliminary efficacy of BEBT-908 for injection in about 20-40 subjects with non-Hodgkin's malignant lymphoma. In this stage, all dose groups were administered continuously for 2 weeks and stopped for 1 week for a total of 21 days，until the disease progresses or withdraws.
Participants will need to understand the requirements and risks of the trial, sign an informed consent form, accept the dosing regimen required by the trial protocol, and follow the investigator's guidance.
- Being tested
- BEBT-908 for injection
- Keywords
- BEBT-908 for injection, Safety, Tolerability, Pharmacokinetics, Effectiveness
- Medical subject headings
- Recurrence, Lymphoma, Non-Hodgkin, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEBT-908 for injectionDrug
Also called CUDC-908
Dose escalation phase：10 or 15、22.5、33.75、45mg/m2, intravenous drip, firstly single dose, after the observation period, the drug was administered continuously for 1 cycle (21 days), 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week.
Dose expansion phase：15 or 22.5mg/m2，intravenous drip, 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week，21 days as cycle.
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy group 1(Dose escalation phase) | Experimental | BEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 10mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. Receives: Drug: BEBT-908 for injection |
| Monotherapy group 2(Dose escalation phase) | Experimental | BEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 15mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. Receives: Drug: BEBT-908 for injection |
| Monotherapy group 3(Dose escalation phase) | Experimental | BEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 22.5mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. Receives: Drug: BEBT-908 for injection |
| Monotherapy group 4(Dose escalation phase) | Experimental | BEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 33.75mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. Receives: Drug: BEBT-908 for injection |
| Monotherapy group 5(Dose escalation phase) | Experimental | BEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 45mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. Receives: Drug: BEBT-908 for injection |
| Monotherapy group 6（Dose expansion phase） | Experimental | BEBT-908 for injection ，dosage form ：Injection ；specification: 25mg , administration method: 15mg/m2，intravenous drip, 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week，21 days as cycle, until the disease progressed or withdrew. Receives: Drug: BEBT-908 for injection |
| Monotherapy group 7（Dose expansion phase） | Experimental | BEBT-908 for injection ，dosage form ：Injection ；specification: 25mg , administration method: 22.5mg/m2，intravenous drip, 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week，21 days as cycle, until the disease progressed or withdrew. Receives: Drug: BEBT-908 for injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Dose-limiting toxicity
Measured: Dose escalation phase: a 6-day observation after a single administration, cycle 1st of continuous medication (21 days). Dose expansion phase: from date of administration until the date of disease progression or withdrawal, assessed up to 36 months.
MTD
Maximum tolerated dose
Measured: Dose escalation phase: a 6-day observation after a single administration, cycle 1st of continuous medication (21 days). Dose expansion phase: from date of administration until the date of disease progression or withdrawal, assessed up to 36 months.
Secondary outcomes (11)
AE
Adverse Event
Measured: From the first administration of the study drug to 30 days after the last administration of the study drug.
Cmax
Peak Plasma Concentration
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
Tmax
Time of peak Plasma Concentration
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
t1/2
Half-life of plasma drug concentrations
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
AUC0-24h
Area under the blood concentration time curve from 0 to 24 hours after administration
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
AUC0-last
Area under the blood concentration time curve from time zero to the last dose
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
CL/F
Apparent total plasma clearance
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
Vd
Apparent volume of distribution
Measured: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
ORR
Objective response rate
Measured: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
DCR
disease control rate
Measured: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
PFS
progression-free survival
Measured: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2023
- Study start2 Mar 2016
- Primary completion8 Mar 2019
- Study completion8 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeBetter Med Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hui Zhou, Phd, Principal investigator, Hunan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06082596
- Sponsor's protocol ID
- GBMT-908-P01
- Status last verified
- Oct 2023
- First submitted
- 9 Oct 2023
- Last updated
- 13 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open, Phase I Clinical Study of BEBT-908 for Injection in the Treatment of Relapsed Refractory Malignant Lymphoma, Multiple Myeloma and Chronic Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT06082596
- Acronym / sponsor ID
- GBMT-908-P01
- Keywords
- BEBT-908 for injection, Safety, Tolerability, Pharmacokinetics, Effectiveness
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- BeBetter Med IncIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2016 (actual)
- Primary completion
- 8 Mar 2019 (actual)
- Study completion
- 8 Mar 2019 (actual)
- First posted
- 13 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the safety and tolerance of BEBT-908 for injection in the treatment of recurrent refractory malignant lymphoma, multiple myeloma and chronic lymphoblastic leukemia, and to obtain the pharmacokinetic data and preliminary efficacy of BEBT-908 for injection, and to explore the relationship between the safety and efficacy of BEBT-908 for injection and related biomarkers.
Detailed description
This study is divided into two stages: dose increasing stage and expanding into the group.
Dose escalation phase: The initial dose was 10mg/m2, and the subsequent dose group was increased by 100% until the first case of grade 2 non-blood toxicity or grade 3 hematological toxicity related to the test drug and no dose-limiting toxicity, then the dose was increased by 50%, and a total of 5 dose groups were designed. In this stage, all subjects received a single dose first and were observed for 6 days. After the end of the observation period, if the subjects were safely tolerant to a single dose，then will receive the same dose of treatment for a cycle, administration regimen is 3 times a week, continuous administration for 2 weeks, withdrawal for 1 week, a total of 21 days as a cycle.
Dose expansion phase: according to the results of pharmacokinetics, safety and efficacy of BEBT-908 for injection obtained in the dose escalation phase, we plan to select two doses to further observe the safety, pharmacokinetic characteristics and preliminary efficacy of BEBT-908 for injection in about 20-40 subjects with non-Hodgkin's malignant lymphoma. In this stage, all dose groups were administered continuously for 2 weeks and stopped for 1 week for a total of 21 days，until the disease progresses or withdraws.
Participants will need to understand the requirements and risks of the trial, sign an informed consent form, accept the dosing regimen required by the trial protocol, and follow the investigator's guidance.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Monotherapy group 1(Dose escalation phase) | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 10mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. |
| Monotherapy group 2(Dose escalation phase) | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 15mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. |
| Monotherapy group 3(Dose escalation phase) | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 22.5mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. |
| Monotherapy group 4(Dose escalation phase) | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 33.75mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. |
| Monotherapy group 5(Dose escalation phase) | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection， dosage form ：Injection； specification: 25 mg , administration method: 45mg/m2，intravenous drip, firstly the subjects were given a single dose and observed for 6 days. At the end of the observation period, if the subjects were tolerant to a single dose and safe, they would receive the same dose for a cycle (21 days), giving the drug three times a week for 2 weeks and stopping the drug for 1 week. A total of 21 days is a cycle. |
| Monotherapy group 6（Dose expansion phase） | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection ，dosage form ：Injection ；specification: 25mg , administration method: 15mg/m2，intravenous drip, 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week，21 days as cycle, until the disease progressed or withdrew. |
| Monotherapy group 7（Dose expansion phase） | Experimental | Drug: BEBT-908 for injectionBEBT-908 for injection ，dosage form ：Injection ；specification: 25mg , administration method: 22.5mg/m2，intravenous drip, 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week，21 days as cycle, until the disease progressed or withdrew. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (43 listed)
- Dose escalation phase:
- Absolute neutrophil count (ANC) ≥ 1000 /μL (if recent bone marrow biopsies or smears prove tumor progression, this index can be < 1000/μL).
- Hemoglobin (HGB) ≥ 9g/dL.
- Platelet count (PLT) ≥ 1000000/μL (if recent bone marrow biopsies or smears prove tumor progression, this index can be < 1000000/μL).
- In patients with serum bilirubin ≤ 1.5 ×upper limit of normal value (ULN) or Gilbert syndrome, the total bilirubin is less than 3.0 × ULN and direct bilirubin is within the normal range.
Key exclusion criteria (69 listed)
- Dose escalation phase:
- Note 1: subjects who began to receive erythropoietin or daipotene within 2 weeks before entering the group can be enrolled in the group.
- Note 2: if used to treat diseases other than lymphoma, such as rheumatoid arthritis, rheumatic polymyalgia, adrenocortical dysfunction or asthma, subjects can receive a maximum daily dose of 10mg with a stable dose of prednisone.
- Note 3: includes any of the following: left ventricular ejection fraction (LVEF) found by cardiac radionuclide scanning (Multigated Radionuclide Angiography (MUGA) ) or echocardiography (ECHO) < 45% Fridericia corrected QT (between QTcF ) > 450ms (QTcF formula); unstable angina pectoris; symptomatic pericarditis; abnormal recording of the left ventricular wall in areas with persistent elevated myocardial enzymes or persistent LVEF function measurements in the past 6 months of myocardial infarction. Has a history of congestive heart failure (New York College of Cardiology Cardiac function Classification III-IV), has a record of cardiomyopathy.
- Note 4: a detailed assessment of the history and risk factors of hepatitis B / C must be performed on all subjects during screening. In screening all subjects with positive medical history, quantitative detection of hepatitis B virus deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) was needed based on risk factors and previous confirmation of hepatitis B/C virus infection. Hepatitis B/C virus replication within the normal range can be included in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BEBT-908 for injectionAlso: CUDC-908Dose escalation phase：10 or 15、22.5、33.75、45mg/m2, intravenous drip, firstly single dose, after the observation period, the drug was administered continuously for 1 cycle (21 days), 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week. Dose expansion phase：15 or 22.5mg/m2，intravenous drip, 3 times a week, continuous administration for 2 weeks and withdrawal for 1 week，21 days as cycle. | Drug | Monotherapy group 1(Dose escalation phase), Monotherapy group 2(Dose escalation phase), Monotherapy group 3(Dose escalation phase), Monotherapy group 4(Dose escalation phase), Monotherapy group 5(Dose escalation phase), Monotherapy group 6（Dose expansion phase）, Monotherapy group 7（Dose expansion phase） |
Primary outcome
DLT
Time frame: Dose escalation phase: a 6-day observation after a single administration, cycle 1st of continuous medication (21 days). Dose expansion phase: from date of administration until the date of disease progression or withdrawal, assessed up to 36 months.
Dose-limiting toxicity
MTD
Time frame: Dose escalation phase: a 6-day observation after a single administration, cycle 1st of continuous medication (21 days). Dose expansion phase: from date of administration until the date of disease progression or withdrawal, assessed up to 36 months.
Maximum tolerated dose
11 secondary outcomes
AE
Time frame: From the first administration of the study drug to 30 days after the last administration of the study drug.
Cmax
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
Tmax
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
t1/2
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
AUC0-24h
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
AUC0-last
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
CL/F
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
Vd
Time frame: Day 1 and Day 12 of cycle 1 before and within 24 hours after administration (each cycle is 21 days).
ORR
Time frame: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
DCR
Time frame: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
PFS
Time frame: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hui Zhou, Phd principal investigator
Hunan Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BEBT-908 for injection in people with Relapsed or Refractory Non-Hodgkin's Lymphoma and Relapsed or Refractory Multiple Myeloma, run by BeBetter Med Inc at 1 site in China.
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 43 inclusion and 69 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 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 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.
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?
DLT (time frame: Dose escalation phase: a 6-day observation after a single administration, cycle 1st of continuous medication (21 days). Dose expansion phase: from date of administration until the date of disease progression or withdrawal, assessed up to 36 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2023.