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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 : Not yet recruiting
First Posted : December 25, 2018
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

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

Condition or disease Intervention/treatment Phase
Lymphoma Drug: HMPL-689 Phase 1 Phase 2

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, including:


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Treatment
All patients take HMPL-689 taken daily
Drug: HMPL-689
HMPL-689 is a PI3Kδ inhibitor




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786926


Contacts
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Contact: John Kauh, MS 9735673151 johnk@hmplglobal.com
Contact: Alisha Khullar, MS 9732873081 alishak@hmplglobal.com

Locations
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United States, Arkansas
Highlands Oncology Group Not yet recruiting
Rogers, Arkansas, United States, 72758
Contact: Patrick Travis    479-936-9900      
Principal Investigator: Patrick Travis, MD         
United States, California
Compassionate Care Research Group, Inc. Recruiting
Fountain Valley, California, United States, 92708
Contact: Barbara Lepthien    714-698-0300    barbaraL@compcareresearch.com   
Principal Investigator: Haresh Jhangiani, MD         
United States, Georgia
Winship Cancer Institute of Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Jonathan Cohen, MD    404-778-1868      
Principal Investigator: Jonathan Cohen, MD         
United States, North Carolina
Levine Cancer Institute- Atrium Health Not yet recruiting
Charlotte, North Carolina, United States, 28204
Contact: Nilanjan Ghosh, MD    980-442-4363      
Principal Investigator: Nilanjan Ghosh, MD         
United States, Texas
Mays Cancer Center, UT Health San Antonio, MD Anderson Cancer Center Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Tracy Rodriguez    210-450-1950    rosdriguezT1@uthscsa.edu   
Principal Investigator: Adolfo Enrique Diaz, MD         
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: John Kauh Hutchison MediPharma

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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT03786926     History of Changes
Other Study ID Numbers: 2018-689-00US1
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hutchison Medipharma Limited:
CLL
SLL
FL
MZL
LPL
WM
MCL

Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases