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

NCT04356846 | Unknown Phase 1 FDA Drug

• 1 other identifier: LP-108-I-01
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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). 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

Outcome Measures

Primary Outcomes (6)

• 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.

  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

  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.

  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.

  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

  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

  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

  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)

  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.

Study Arms (2)

R/R CLL

EXPERIMENTAL

Relapsed or Refractory Chronic Lymphocytic Leukemia Patients

Drug: LP-108 tablet

R/R NHL

EXPERIMENTAL

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma Patients, including SLL, FL, MZL, MCL, DLBCL, WM.

Drug: LP-108 tablet

Interventions

LP-108 tablet DRUG

Taken orally within 30 minutes after a meal at the designated dose, once daily.

R/R CLL; R/R NHL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Guangzhou Lupeng Pharmaceutical Company LTD.: collaborator
• Newave Pharmaceutical Inc: collaborator

Study Sites (1)

the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jianyong Li, Ph.D.

CONTACT

025-83718836; lijianyonglm@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2020
• First Posted: April 22, 2020
• Study Start: May 1, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 1, 2023

Record last verified: 2023-04

Locations

CN (1)