Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

NCT ID: NCT03786926

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-26
• Study Completion Date: 2024-06-26

Brief Summary

An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas

Detailed Description

This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients with relapsed or refractory lymphoma.

HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling pathway

This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage (Stage 2).

Dose Escalation Stage (Stage 1):

This stage will end when any of the following criteria is met:

• The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities (DLTs) are observed out of the first 3 patients at dose level 1.
• The maximum sample size is reached.
• The MTD and/or RP2D is confirmed.

Dose Expansion Stage (Stage 2):

To further characterize the safety and explore the preliminary anti-tumor activity of HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

All patients take HMPL-689 taken daily

Group Type: EXPERIMENTAL

HMPL-689

Intervention Type: DRUG

HMPL-689 is a PI3Kδ inhibitor

Interventions

HMPL-689

HMPL-689 is a PI3Kδ inhibitor

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. (ECOG) performance status of 0 or 1;

2. Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);

3. Patients with relapsed or refractory NHL for whom:

• Standard of care treatment options no longer exist (Stage 1 only);
• Standard of care treatment options no longer exist with the exception of PI3K-delta inhibitors (Stage 2 only);

4. Expected survival of more than 24 weeks.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study entry:

1. Primary central nervous system (CNS) lymphoma;

2. Any of the following laboratory abnormalities Absolute neutrophil count; <1.0×10^9/L, Hemoglobin <80 g/L Platelets <50 ×10^9/L

3. Inadequate organ function, defined by the following:

• Total bilirubin ≥1.5 times the upper limit of normal (× ULN);
• AST or ALT > 2.5 × ULN;
• Estimated creatinine clearance (CrCl) per Cockcroft-Gault;
• Dose Escalation stage of trial (Stage 1) - CrCl < 40 mL/min;
• Dose Expansion stage of trial (Stage 2) - CrCl <30 mL/min;

4. International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin time (aPTT) > 1.5 × ULN;

5. Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN;

6. Patients with presence of second primary malignant tumors within the last 2 years;

7. Clinically significant history of liver disease;

8. Prior treatment with any PI3Kδ inhibitors;

9. Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within 7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to initiation of study treatment, prior autologous transplant within 6 months of study treatment, prior allogenic stem cell transplant within 6 months of study treatment;

10. Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis);

11. Major surgical procedure within 4 weeks prior to initiation of study treatment;

12. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia;

13. New York Heart Association (NYHA) Class II or greater congestive heart failure;

14. Congenital long QT syndrome or QTc >470 msec;

15. Currently use medication known to cause QT prolongation or torsades de pointes;

16. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment;

17. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment;

18. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease;

19. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);

20. Patients with ongoing chronic gastrointestinal diseases;

21. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchmed

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claudia Huang

Role: STUDY_DIRECTOR

Hutchmed Limited

Nilanjan Ghosh, MD

Role: PRINCIPAL_INVESTIGATOR

Atrium Health Levine Cancer Institute

Jonathan B Cohen, MD

Role: PRINCIPAL_INVESTIGATOR

Emory Winship Cancer Institute

Locations

Innovative Clinical Research Institute

Anaheim, California, United States

Pacific Cancer Medical Center

Anaheim, California, United States

Ventura County Hematology-Oncology Specialists

Oxnard, California, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Clinical Research Alliance, Inc

Westbury, New York, United States

Levine Cancer Institute- Atrium Health

Charlotte, North Carolina, United States

Baylor Scott and White Research Institute

Dallas, Texas, United States

Renovatio Clinical

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Medical Oncology Associates, P.S.

Spokane, Washington, United States

Helsingin yliopistollinen keskussairaala

Helsinki, , Finland

Tampereen yliopistollinen sairaala

Tampere, , Finland

Hopital Henri Mondor

Créteil, Val De Marne, France

CHU de Nantes - Hotel Dieu

Nantes, , France

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, , France

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, , Italy

Ospedale San Raffaele

Milan, , Italy

KO-MED Centra Kliniczne

Biała Podlaska, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

BioResearch Group Sp. Z. o. o.

Krakow, , Poland

NASZ LEKARZ Osrodek Badan Klinicznych

Torun, , Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego

Wroclaw, , Poland

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Countries

United States; Finland; France; Italy; Poland; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-689-00US1

Identifier Type: -

Identifier Source: org_study_id