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

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hutchison Medipharma Limited

Criteria

Inclusion Criteria:

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

2. Histologically confirmed lymphoma (tumor types are restricted to CLL, SLL, FL, MZL, LPL/WM, and MCL.)

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 <1.5×10^9/L, Hemoglobin <90 g/L Platelets <100 ×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 < 50 mL/min

• Dose Expansion stage of trial (Stage 2) - CrCl <30 mL/min

4. Clinically significant history of liver disease,

5. Prior treatment with any PI3Kδ inhibitors

6. 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,

7. Clinically significant active infection

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

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

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

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

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

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

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

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

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

17. History of drug induced pneumonitis