A Phase I Study of LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma

April 28, 2023 updated by: The First Affiliated Hospital with Nanjing Medical University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
74

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • The First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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;
    • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: R/R CLL
Relapsed or Refractory Chronic Lymphocytic Leukemia Patients
Drug: LP-108 tablet
Taken orally within 30 minutes after a meal at the designated dose, once daily.
Experimental: R/R NHL
Relapsed or Refractory B-cell Non-Hodgkin Lymphoma Patients, including SLL, FL, MZL, MCL, DLBCL, WM.
Drug: LP-108 tablet
Taken orally within 30 minutes after a meal at the designated dose, once daily.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
Time Frame: From first dose of study drug administration until 30 days after study drug discontinue.
Safety Proflie
From first dose of study drug administration until 30 days after study drug discontinue.
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.
Up to Week 37 for LP-108.
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.
Up to Week 37 for LP-108.
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
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
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Tumor response or clinical disease progression
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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The First Affiliated Hospital with Nanjing Medical University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Guangzhou Lupeng Pharmaceutical Company LTD.
Newave Pharmaceutical Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 10, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 22, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 1, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LP-108-I-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings