Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS… (NCT04771572) | Clinical Trial Compass
RecruitingPhase 1
Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS/MPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.
United States100 participantsStarted 2022-05-08
Plain-language summary
This is a Phase 1, multi-center, open-label study with a dose-escalation phase (Phase 1a) and a cohort expansion phase (Phase 1b), to evaluate the safety, tolerability, and PK profile of LP-118 under a once daily oral dosing schedule in up to 100 subjects.
Who can participate
Age range13 Years
SexALL
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Male or female subjects, ≥ 18 years of age at the time of Screening with the following exception as outlined below:
✓For T cell and B cell ALL subjects with age between 13 - 18 years, their body weight shall be ≥ 40 kg.
✓. Eligible subject must have an advanced hematologic malignancy including:
✓. For Group 1d ALL subjects only, white blood cell (WBC) count ≤ 25 × 109 cells/L at the time of enrollment (glucocorticoids or hydroxyurea is permitted to control WBC count prior to and during therapy).
✓. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
✓. Adequate cardiac function defined as shortening fraction of ≥ 40% by 2D echocardiogram without Doppler.
✓. Subject must have adequate bone marrow (independent of growth factor support), coagulation, renal, and hepatic function, per laboratory reference ranges at Screening as follows:
✓. Females of childbearing potential (i.e., non-postmenopausal for at least 2 years or surgically sterile) and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 90 days after discontinuing study drug:
Exclusion criteria
✕. Subjects who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Subjects in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is permitted.
What they're measuring
1
Maximum Tolerated Dose (MTD)
Timeframe: At the end of cycle 1 (each cycle is 28 days)
2
Recommended Phase 2 Dose (RP2D) or Optimal Biological Dose (OBD)
Timeframe: At the end of cycle 1 (each cycle is 28 days)
3
Pharmacokinetic (PK) profile of LP-118: Maximum Plasma Concentration (Cmax)
Timeframe: At Cycle 0 Day 1, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 (28-day cycles))
4
Pharmacokinetic (PK) profile of LP-118: Area Under the Curve (AUC) of LP-118
Timeframe: At Cycle 0 Day 1, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 (28-day cycles)
5
Pharmacokinetic (PK) profile of LP-118: Time at Maximum Concentration (Tmax) of LP-118
Timeframe: At Cycle 0 Day 1, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 (28-day cycles)
✕. Subject has a history of other malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with the exception below.
✕. Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous therapy (excluding neuropathy):
✕. Subject has received the following medications, therapies, or natural products within 7 days prior to the first dose of LP-118:
✕. Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect his/her participation in this study. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the study, place the subject at unacceptable risk or interfere with the interpretation of the results. For subjects who have required surgical intervention for any above diseases within the past 6 months, a discussion with the Investigator and the Medical Monitor is needed.
✕. Subject has baseline prolongation of the heart rate-corrected QT (QTcF) interval ≥ 480 ms (calculated per Fridericia's formula \[QTcF = QT/RR (1/3)\])), a cardiovascular disability status of New York Heart Association Class ≥ 2 or associated other significant screening ECG or ultrasonic cardiogram abnormalities, per Investigator's judgement. For any subject with underlying RBBB or LBBB, cardiology review is needed to correct QTcF calculation using Sponsor recommended formula.
✕. Subject has significant a history of congenital long QT syndrome or Torsades de Pointes (TdP), uncontrolled or symptomatic arrhythmias, congestive heart failure, myocardial infarction, stroke, or intracranial hemorrhage within 6 months prior to the first dose of LP-118.
✕. Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: