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Brief Title: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma
Official Title: A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Patients With Relapsed or Refractory Lymphoma
Study ID: NCT03779113
Brief Summary: This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients with relapsed or refractory lymphoma who have exhausted approved therapy options. This study consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).
Detailed Description: This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients with relapsed or refractory lymphoma who have exhausted approved therapy options. This study consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2). Dose Escalation Stage (Stage 1) Dosing will begin at 100 mg once daily (QD). A cycle of study treatment will be defined as 28 days of continuous dosing. The modified 3+3 design will be applied for dose escalation and MTD determination to limit the number of patients exposed to potentially ineffective or unsafe doses. The study will enroll 1 patient and the patient will be treated for a 28-day cycle in the initial dose cohort. If there is no Dose Limiting Toxicity (DLT) and no more than 2 treatment-emergent adverse events (TEAEs) of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 in the first treatment cycle, the study will be escalated to the next dose cohort and continue with the standard 3+3 design. Otherwise, the trial will revert to a standard 3+3 design from the initial dose cohort. A minimum of 3 patients will be enrolled and observed for toxicity in each successive dose cohort after the initial dose cohort. If the 3 patients initially enrolled in a given dose cohort complete the DLT assessment window (Cycle 1, Days 1-28) without experiencing a DLT, 3 patients will be enrolled at the next higher dose level. If 2 or more of the initial 3 patients enrolled at any dose level experience a DLT during the DLT assessment window, the dose escalation will be halted. If 1 of the initial 3 patients enrolled at any dose level experiences a DLT during the DLT assessment window, additional patients will be enrolled at that dose level for a minimum of 6 evaluable patients for DLT. If a DLT is observed in 1 of the 6 valuable patients at this dose level, dose escalation will proceed to the next pre- defined dose level. If DLTs are observed in 2 or more of the 6 evaluable patients at a given dose level, the dose escalation will be halted. If the dose escalation is completed due to 2 or more DLTs at a dose level and that dose level is ≥50% higher than the previous dose level, then an intermediate dose level may be evaluated for toxicity in the same manner as described above. If the dose level is \<50% higher than the previous dose level, in which only 3 DLT evaluable patients were enrolled, 3 additional patients will be enrolled at that dose level to comprise 6 DLT evaluable patients. The proposed dose escalation scheme comprises Cohorts 1 to 5 with dosing levels of 100 mg QD, 200 mg QD, 400 mg QD, 600 mg QD and 800 mg QD, respectively. The need for dose escalation beyond 800 mg QD, the specific dose to be tested and the potential for twice-daily (BID) dosing will be evaluated jointly by investigators and the sponsor based on the cumulative clinical safety, pharmacokinetic, and preliminary efficacy data. Safety monitoring and evaluation of dose escalation will be carried out by the Safety Review Committee, which will be comprised of the sponsor's study team members (including medical monitor, safety monitor and and Pharmacokinetic scientist) and the site principal investigators. The adverse event profile and serum concentration of HMPL-523 data will be evaluated to determine whether it is safe to continue the assigned HMPL-523 dose for dose escalation or whether the dose should be de-escalated to the lower dose level. Dose Expansion Stage (Stage 2) The adverse event profile, serum concentration, and preliminary anti-tumor activity of HMPL-523 at the maximum tolerated dose(MTD)/recommended phase 2 dose(RP2D) will be further evaluated in approximately 50 patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphomas. The tumor types of the dose expansion stage are restricted to: * 10 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma * 20 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma post-BTK exposure * 10 patients with mantle cell lymphoma * 20 patients with follicular lymphoma (Grade 1-3a) * 10 patients with marginal zone lymphoma * 10 patients with waldenström's macroglobulinemia/lymphoplasmacytic lymphoma * 10 patients with peripheral T- cell lymphoma * 10 patients with cutaneous B-cell lymphoma * 10 patients with hodgkin lymphoma Patients will receive HMPL-523 at the MTD/RP2D for continuous 28-day treatment cycles until disease progression, death, intolerable toxicity, at investigator's discretion that the patient can no longer benefit from the study treatment, patient withdrawal from the study, or the end of study, whichever comes first.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
Pacific Cancer Medical Center, Inc., Anaheim, California, United States
Innovative Clinical Research Institute, Downey, California, United States
Ventura County Hematology-Oncology Specialists, Oxnard, California, United States
Summit Medical Group, Florham Park, New Jersey, United States
Clinical Research Alliance, New Hyde Park, New York, United States
Leo Jenkins Cancer Center/ECU School of Medicine, Greenville, North Carolina, United States
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Renovatio Clinical, The Woodlands, Texas, United States
Aarhus University Hospital, Aarhus, , Denmark
Helsingin yliopistollinen keskussairaala, Helsinki, , Finland
Tampereen yliopistollinen sairaala, Tampere, , Finland
CHU Clermont Ferrand - Hôpital d'Estaing, Clermont-Ferrand, , France
Hôpital Henri Mondor, Créteil, , France
Groupe Hospitalier Pitie-Salpetriere, Paris, , France
CHU Poitiers - Hôpital la Milétrie, Poitiers, , France
Ospedale San Raffaele, Milan, Milano, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII), Bergamo, , Italy
Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo), Monza, , Italy
KO-MED Centra Kliniczne, Biała Podlaska, , Poland
Uniwersyteckie Centrum Kliniczne, Gdańsk, , Poland
Nasz Lekarz Przychodnie Medyczne, Toruń, , Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego, Wrocław, , Poland
Hospital Universitari Vall d'Hebron, Barcelona, , Spain
ICO Badalona - Hospital Universitari Germans Trias i Pujol, Barcelona, , Spain
Institut Català d'Oncologia, Barcelona, , Spain
Hospital Universitario Ramon y Cajal, Madrid, , Spain
Fundacion Jimenez Diaz, Madrid, , Spain
Hospital Universitario Infanta Leonor, Madrid, , Spain
Hospital Universitario Quironsalud Madrid, Madrid, , Spain
MD Anderson Cancer Centre, Madrid, , Spain
Hospital Universitario Virgen Macarena, Sevilla, , Spain
Hospital Universitario Virgen del Rocio, Seville, , Spain
Name: Vijay Jayaprakash, MD
Affiliation: Hutchmed
Role: STUDY_DIRECTOR