Clinical Trials /

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

NCT03786926

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

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Leukemia
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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-US001
  • NCT ID: NCT03786926

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
HMPL-689Treatment

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

NameTypeDescriptionInterventions
TreatmentExperimentalAll patients take HMPL-689 taken daily
  • HMPL-689

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: anti-neoplastic 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, monoclonal antibody within 3 weeks
             of treatment, any use of anti-cancer vaccine, prior administration of
             radioimmunotherapy within 3 months of study treatment, any use of strong CYP3A4
             induces within 7 days 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

  • CLL
  • SLL
  • FL
  • MZL
  • LPL
  • WM
  • MCL

Last Updated

October 8, 2019