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Trial record 1 of 1 for:    HMPL-689 | Krakow, Poland
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Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

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ClinicalTrials.gov Identifier: NCT03786926
Recruitment Status : Recruiting
First Posted : December 26, 2018
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE December 18, 2018
First Posted Date  ICMJE December 26, 2018
Last Update Posted Date October 10, 2019
Actual Study Start Date  ICMJE August 26, 2019
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2018)
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 ]
The safety and tolerability of HMPL-689 dose will be evaluated based on adverse events data
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2018)
  • 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) ]
    To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma
  • 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) ]
    To characterize the pharmacokinetic (PK) properties of HMPL-689 in patients with relapsed or refractory lymphoma
  • 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 ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE Drug: HMPL-689
HMPL-689 is a PI3Kδ inhibitor
Study Arms  ICMJE Experimental: Treatment
All patients take HMPL-689 taken daily
Intervention: Drug: HMPL-689
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 23, 2018)
85
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tunde Lawrence, MD, PhD 9737862789 tundel@hmplglobal.com
Contact: Alisha Khullar, MS 9732873081 alishak@hmplglobal.com
Listed Location Countries  ICMJE Poland,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03786926
Other Study ID Numbers  ICMJE 2018-689-US001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tunde Lawrence, MD, PhD Hutchison Medipharma Limited
Principal Investigator: Nilanjan Ghosh, MD Levine Cancer Institute
Principal Investigator: Jonathan B Cohen, MD Emory Winship Cancer Institute
PRS Account Hutchison Medipharma Limited
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP