Non-Hodgkin LymphomaPhase 1NCT04356846
A Phase I Study of LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma
A Phase 1 study testing LP-108 tablet in people with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This study is a multi-center, open-label, single-arm phase I clinical study of LP-108. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL, arm A) and other B cell non-Hodgkin's lymphoma (NHL, Arm B). Each arm has a dose escalation phase (phase Ia) and expansion phase (phase Ib). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- What is being tested?
- LP-108 tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2020to 1 Dec 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Per 2017 revised WHO lymphoma classification criteria, subject must have either:
- (Arm A) Diagnosed with relapsed or refractory CLL and require treatment in the opinion of the Investigator.
- (Arm B) Diagnosed with relapsed or refractory non-Hodgkin's lymphoma associated with B-cell proliferation (such as SLL \ MCL \ FL \ MZL \ DLBCL \ WM, etc.) in need of treatment.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1.
- Subject must have adequate bone marrow function independent of growth factor support per local laboratory reference range at Screening.
- Subject must have adequate coagulation, renal, and hepatic function, per local laboratory reference range at Screening.
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- All acute toxicity from previous anti-tumor treatment or surgery has been alleviated to NCI CTCAE 5.0 ≤ Grade 1.
- All enrolled patients should take medically approved contraceptives during the entire treatment period and within 90 days after the end of treatment.
- Subjects must be willing to provide valid diagnostic evidence or accept bone marrow biopsy before treatment and accept bone marrow biopsy after treatment start.
- Patients with NHL who have undergone autologous stem cell transplantation must complete the transplantation operation for more than 6 months when enrolled, and have sufficient bone marrow function without relying on growth factor stimulation.
- Volunteer and sign informed consent, willing to follow trial protocol.
Who cannot join
- According to the 2017 revised WHO Lymphoma Classification Criteria, patients diagnosed with the following diseases: Burkitt lymphoma or Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, and post-transplant lymphoproliferative disease(PTLD) .
- Previously received other BCL-2 protein family inhibitors.
- CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL subject has undergone an allogeneic stem cell transplant.
- Subjects who have received the following treatments within 4 weeks or 5 half-lives before the first dose of LP-108:
- Antitumor therapies including myelosuppressive chemotherapy, targeted therapy, biological therapy and / or immunotherapy;
- Any investigational treatment;
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- Patients who have undergone major surgery, severe trauma or radiotherapy.
- Subjects who have received the following treatments within 2 weeks before the first dose of LP-108:
- Steroids or traditional herbal medicine for antitumor purposes;
- Strong and moderate CYP3A4/5 inhibitors and inducers, P-gp inhibitors and CYP2C8 sensitive substrates;
- All drugs that may cause QTc interval prolongation or torsional tachycardia.
- Have had malignancies other than the indications targeted in this study in the past three years, except for basal cell carcinoma of the skin and cervical carcinoma in situ treated radically.
- Any serious and / or uncontrolled systemic disease.
- Poor cardiovascular function, in line with New York Heart Association (NYHA) cardiac function classification ≥ 2 or QTcF greater than 480ms on ≥ 3 independent ECG.
- Disease states where clinical manifestations may be difficult to control, including
- HIV, HBV, HCV, syphilis positive or active bacterial and fungal infections;
- Disease affects the central nervous system with obvious symptoms;
- Autoimmune hemolytic anemia or Idiopathic thrombocytopenic purpura.
- Any gastrointestinal conditions that may severely affect the study drug absorption or pharmacokinetic parameters.
- Patients who were unable to discontinue taking CYP2C8 substrate repaglinide to control type 2 diabetes during the study.
- Subjects who cannot tolerate urine collection, venipuncture, lymph node biopsy, and bone marrow aspiration.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210000
Jianyong Li, PhD, lijianyonglm@126.com
About this study
Official title: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the Oral BCL-2 Inhibitor LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma
This study is a multi-center, open-label, single-arm phase I clinical study of LP-108. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL, arm A) and other B cell non-Hodgkin's lymphoma (NHL, Arm B). Each arm has a dose escalation phase (phase Ia) and expansion phase (phase Ib). During the dose escalation phase, the primary objectives are to define dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and to explore a recommended phase II dose. Dose escalation is based on the classic "3 + 3" design, while accelerated titration is applied to the initial lower doses. After the RP2Ds are determined, additional patients will be enrolled in the expansion phase to further evaluation the safety, PK and preliminary efficacy of LP-108, each therapy can enroll 12-20 subjects.
- Conditions
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Being tested
- LP-108 tablet
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LP-108 tabletDrug
Taken orally within 30 minutes after a meal at the designated dose, once daily.
| Study group | Role | What they receive |
|---|---|---|
| R/R CLL | Experimental | Relapsed or Refractory Chronic Lymphocytic Leukemia Patients Receives: Drug: LP-108 tablet |
| R/R NHL | Experimental | Relapsed or Refractory B-cell Non-Hodgkin Lymphoma Patients, including SLL, FL, MZL, MCL, DLBCL, WM. Receives: Drug: LP-108 tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RP2D), and lead-in period regimen
Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
Measured: Lead-in period (0-4 weeks) plus 3 weeks of study drug administration at the designated cohort dose.
Number of subjects with adverse events and its frequency
Safety Proflie
Measured: From first dose of study drug administration until 30 days after study drug discontinue.
Determination of plasma peak concentration (Cmax) of LP-108
Blood and urine samples for pharmacokinetic analysis of LP-108 will be collected at designated time points.
Measured: Up to Week 37 for LP-108.
Determination of Area Under the Curve (AUC) of LP-108
Blood and urine samples for pharmacokinetic analysis of LP-108 will be collected at designated time points.
Measured: Up to Week 37 for LP-108.
Food Effect - Cmax
Blood samples for food effect pharmacokinetic analysis of LP-108 will be collected at designated time points
Measured: Pharmacokinetic (PK) parameter Cmax (maximum plasma concentration of LP-108) between each diet (LP-108 under fasting versus fed conditions)，up to week 8 for LP-108.
Food Effect - AUC
Blood samples for food effect pharmacokinetic analysis of LP-108 will be collected at designated time points
Measured: Pharmacokinetic (PK) parameter AUC (area under the curve of LP-108) between each diet (LP-108 under fasting versus fed conditions)，up to week 8 for LP-108.
Secondary outcomes (2)
Preliminary efficacy assessment
Tumor response or clinical disease progression
Measured: Designated dose starting week for clinical disease progression and tumor response; and every 4-12 weeks thereafter until the date of first documented progression or date of death from any cause, whichever came first,.assessed up to 24 months.
Minimal residual disease (MRD)
MRD assessed in the peripheral blood and/or bone marrow (BM) either by four color flow cytometry or NGS, will be measured in CLL subjects achieving CR/CRi.
Measured: At least 2 months after the CR, CRi criteria for tumor response are first met. Measured up to 24 months after the last subject has enrolled in the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start1 May 2020
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- 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
- 74 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Guangzhou Lupeng Pharmaceutical Company LTD., Newave Pharmaceutical Inc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04356846
- Sponsor's protocol ID
- LP-108-I-01
- Status last verified
- Apr 2023
- First submitted
- 10 Apr 2020
- Last updated
- 1 May 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the Oral BCL-2 Inhibitor LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT04356846
- Acronym / sponsor ID
- LP-108-I-01
- Conditions
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- Guangzhou Lupeng Pharmaceutical Company LTD., Newave Pharmaceutical Inc
- Study start
- 1 May 2020 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 22 Apr 2020 (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.
This study is a multi-center, open-label, single-arm phase I clinical study of LP-108. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL, arm A) and other B cell non-Hodgkin's lymphoma (NHL, Arm B). Each arm has a dose escalation phase (phase Ia) and expansion phase (phase Ib). During the dose escalation phase, the primary objectives are to define dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and to explore a recommended phase II dose. Dose escalation is based on the classic "3 + 3" design, while accelerated titration is applied to the initial lower doses. After the RP2Ds are determined, additional patients will be enrolled in the expansion phase to further evaluation the safety, PK and preliminary efficacy of LP-108, each therapy can enroll 12-20 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| R/R CLL | Experimental | Drug: LP-108 tabletRelapsed or Refractory Chronic Lymphocytic Leukemia Patients |
| R/R NHL | Experimental | Drug: LP-108 tabletRelapsed or Refractory B-cell Non-Hodgkin Lymphoma Patients, including SLL, FL, MZL, MCL, DLBCL, WM. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Per 2017 revised WHO lymphoma classification criteria, subject must have either:
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1.
- Subject must have adequate bone marrow function independent of growth factor support per local laboratory reference range at Screening.
- Subject must have adequate coagulation, renal, and hepatic function, per local laboratory reference range at Screening.
- All acute toxicity from previous anti-tumor treatment or surgery has been alleviated to NCI CTCAE 5.0 ≤ Grade 1.
Key exclusion criteria (21 listed)
- According to the 2017 revised WHO Lymphoma Classification Criteria, patients diagnosed with the following diseases: Burkitt lymphoma or Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, and post-transplant lymphoproliferative disease(PTLD) .
- Previously received other BCL-2 protein family inhibitors.
- CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL subject has undergone an allogeneic stem cell transplant.
- Subjects who have received the following treatments within 4 weeks or 5 half-lives before the first dose of LP-108:
- Subjects who have received the following treatments within 2 weeks before the first dose of LP-108:
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 |
|---|---|---|
| LP-108 tabletTaken orally within 30 minutes after a meal at the designated dose, once daily. | Drug | R/R CLL, R/R NHL |
Primary outcome
Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RP2D), and lead-in period regimen
Time frame: Lead-in period (0-4 weeks) plus 3 weeks of study drug administration at the designated cohort dose.
Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
Number of subjects with adverse events and its frequency
Time frame: From first dose of study drug administration until 30 days after study drug discontinue.
Safety Proflie
Determination of plasma peak concentration (Cmax) of LP-108
Time frame: Up to Week 37 for LP-108.
Blood and urine samples for pharmacokinetic analysis of LP-108 will be collected at designated time points.
Determination of Area Under the Curve (AUC) of LP-108
Time frame: Up to Week 37 for LP-108.
Blood and urine samples for pharmacokinetic analysis of LP-108 will be collected at designated time points.
Food Effect - Cmax
Time frame: Pharmacokinetic (PK) parameter Cmax (maximum plasma concentration of LP-108) between each diet (LP-108 under fasting versus fed conditions)，up to week 8 for LP-108.
Blood samples for food effect pharmacokinetic analysis of LP-108 will be collected at designated time points
Food Effect - AUC
Time frame: Pharmacokinetic (PK) parameter AUC (area under the curve of LP-108) between each diet (LP-108 under fasting versus fed conditions)，up to week 8 for LP-108.
Blood samples for food effect pharmacokinetic analysis of LP-108 will be collected at designated time points
2 secondary outcomes
Preliminary efficacy assessment
Time frame: Designated dose starting week for clinical disease progression and tumor response; and every 4-12 weeks thereafter until the date of first documented progression or date of death from any cause, whichever came first,.assessed up to 24 months.
Minimal residual disease (MRD)
Time frame: At least 2 months after the CR, CRi criteria for tumor response are first met. Measured up to 24 months after the last subject has enrolled in the study.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 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.
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 LP-108 tablet in people with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by The First Affiliated Hospital with Nanjing Medical University 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 11 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 1 May 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jianyong Li, Ph.D. (025-83718836, lijianyonglm@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RP2D), and lead-in period regimen (time frame: Lead-in period (0-4 weeks) plus 3 weeks of study drug administration at the designated cohort dose.). 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?
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 1 May 2023.