Description:
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
Title
- Brief Title: Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas
- Official Title: A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Relapsed or Refractory Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
2018-689-00US1
- NCT ID:
NCT03786926
Conditions
Interventions
Drug | Synonyms | Arms |
---|
HMPL-689 | | Treatment |
Purpose
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment | Experimental | All patients take HMPL-689 taken daily | |
Eligibility 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of adverse events as evaluated by the NCI CTCAE v5.0 grade |
Time Frame: | From first dose to within 30 days after last dose |
Safety Issue: | |
Description: | The safety and tolerability of HMPL-689 dose will be evaluated based on adverse events data |
Secondary Outcome Measures
Measure: | maximum plasma concentration (Cmax) |
Time Frame: | from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days) |
Safety Issue: | |
Description: | To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma |
Measure: | Area under the concentration-time curve in a selected time interval (AUC0-t) |
Time Frame: | from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days) |
Safety Issue: | |
Description: | To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma |
Measure: | Objective response rate (ORR) defined as the proportion of patients who have a CR or PR |
Time Frame: | from first dose to within 30 days of last dose |
Safety Issue: | |
Description: | To evaluate the anti-tumor activity of HMPL-689 in patients with relapsed or refractory lymphoma according to: (1) Chronic Lymphocytic Leukemia (CLL) - modified International Workshop on CLL guidelines, (2) Waldenstrom's Macroglobulinemia (WM) - consensus of international workshops on WM, (3) Lymphomas other than CLL or WM: Lugano Response Criteria for Hodgkin and Non-Hodgkin's Lymphoma |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hutchison Medipharma Limited |
Trial Keywords
Last Updated
February 3, 2021