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An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03779113
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : January 11, 2022
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Brief Summary:
This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients with relapsed or refractory lymphoma who have exhausted approved therapy options. This study consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).

Condition or disease Intervention/treatment Phase
Non Hodgkin Lymphoma Drug: HMPL-523 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Patients With Relapsed or Refractory Lymphoma
Actual Study Start Date : September 26, 2019
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2024

Arm Intervention/treatment
Experimental: Treatment
All patients to received study drug (HMPL-523)
Drug: HMPL-523
Oral HMPL-523

Primary Outcome Measures :
  1. Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: From first dose to within 30 days after the last dose ]
    The safety and tolerability of HMPL-523 will be evaluated based on adverse events data.

Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: From Cycle 1, Day 1, 5 min pre-dose 1st dose until Cycle 1, Day 28 8 hours post-dose. ]
    To Characterize the pharmacokinetic properties of HMPL-523 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, 5 min pre-dose 1st dose until Cycle 1, Day 28 8 hours post-dose. ]
    To characterize the pharmacokinetic properties of HMPL-523 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 after the last dose ]
    To evaluate the anti-tumor activity of HMPL-523 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

Patients must meet the following criteria to be eligible for study entry:

  1. Signed informed consent form (ICF).
  2. Age ≥18 years.
  3. ECOG performance status of 0 or 1.
  4. Histologically confirmed lymphoma, including Hodgkin's lymphoma and non-Hodgkin's lymphoma. In the dose expansion stage, the tumor types may be restricted to any or all of the following tumor types. There may be approximately 10 patients in each cohort depending on response signals suggesting efficacy, except for 2 identified cohorts with approximately 20 patients per cohort: relapsed or refractory CLL/SLL, CLL/SLL post-BTK exposure (n=20), MCL, FL (Grade 1-3a) (n=20), MZL, WM/LPL, PTCL,CBCL, and/or HL
  5. Patients with relapsed or refractory lymphoma who have exhausted all approved therapy options.
  6. In the dose expansion stage, patients must have measurable disease for an objective response assessment, except for patients with CLL and WM/LPL
  7. Availability of tumor sample for patients in dose expansion cohorts: This may be an archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor sample is not available, the Sponsor may waive the requirement after discussion
  8. Expected survival of more than 24 weeks as determined by the investigator.
  9. Male patients must agree to use a condom and female patients of childbearing potential must agree to use highly effective contraceptive measures for 30 days after the last dose of study drug. These include as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, and transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, and implantable), intrauterine contraceptive device, intrauterine hormone release system, bilateral tubal occlusion, or a vasectomized partner, provided that male partner is the sole sexual partner of the female patient. Postmenopausal females (women who have not had menses for at least 1 year without an alternative medical cause) are exempt from this criterion.

Exclusion Criteria

  1. Patients with primary central nervous system (CNS) lymphoma.
  2. Any of the following laboratory abnormalities: Absolute neutrophil count<1.0×10^9/L, Hemoglobin <80 g/L, Platelets <50×10^9/L
  3. Inadequate organ function, defined by the following: Total bilirubin >1.5 times the upper limit of normal (× ULN), aspartate aminotransferase and/or alanine aminotransferase >2.5 × ULN, Estimated Creatinine Clearance (CrCl) per Cockcroft-Gault [Dose Escalation portion of trial (Stage 1) CrCl < 40 mL/min, Dose Expansion portion of trial (Stage 2) CrCl < 30 mL/min], Serum amylase or lipase >ULN, International normalized ratio >1.5 × ULN, or activated partial thromboplastin time >1.5 × ULN
  4. Patients with clinically detectable second primary malignant tumors at enrollment or other malignant tumors within the last 2 years (with the exception of radically treated basal cell or squamous cell carcinoma of the skin, in situ cervix, or in situ breast cancer).
  5. Any anticancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine, or radiotherapy within 3 weeks prior to the initiation of study treatment.
  6. Herbal therapy within 1 week prior to the initiation of study treatment.
  7. Prior use of any anti-cancer vaccine
  8. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)
  9. Prior administration of radioimmunotherapy within 3 months before initiation of study treatment.
  10. Use of strong cytochrome P450 isoform 3A inhibitors and inducers and drugs metabolized by cytochrome P450 isoform 3A, cytochrome P450 isoform 2B6, and cytochrome P450 isoform 1A2, and are identified as narrow therapeutic drugs within 7 days or 3 half-lives, whichever is longer, prior to initiation of study treatment
  11. Adverse events from prior anticancer therapy that have not resolved to Grade ≤1, except for alopecia.
  12. Prior autologous stem cell transplant within 6 months prior to the initiation of study treatment.
  13. Prior allogeneic stem cell transplant within 6 months prior to the initiation of study treatment or with any evidence of active graft versus host disease or requirement for immunosuppressants within 28 days prior to the initiation of study treatment.
  14. Clinically significant active infection (eg, pneumonia).
  15. Major surgical procedure within 4 weeks prior to the initiation of study treatment.
  16. Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
  17. Pregnant (positive serum beta human chorionic gonadotropin test) or lactating women.
  18. New York Heart Association Class II or greater congestive heart failure.
  19. Congenital long QT syndrome or correct QT interval using Fridericia's formula (QTcF) >480 msec
  20. Current use of medication known to cause QT prolongation or Torsades de Pointes
  21. History of myocardial infarction or unstable angina within 6 months prior to the initiation of study treatment.
  22. History of stroke or transient ischemic attack within 6 months prior to the initiation of study treatment.
  23. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease.
  24. Treatment in a clinical study within 30 days prior to the initiation of study treatment.
  25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, or renders the patient at high risk from treatment complications.

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 identifier (NCT number): NCT03779113

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Contact: Vijay Jayaprakash, MD 9739006617
Contact: Rathi Pillai, MD 973-421-5002

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United States, New York
Clinical Research Alliance Recruiting
New Hyde Park, New York, United States, 11042
Contact: Morton Coleman, MD    516-216-1979   
Principal Investigator: Morton Colman, MD         
United States, South Carolina
Greenville Health System Recruiting
Greenville, South Carolina, United States, 29605
Contact: Jill Roemmich    864-455-3600   
Principal Investigator: Elizabeth Cull, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Gloria Martinez    877-632-6789   
Principal Investigator: Paolo Strati, MD         
Helsingin yliopistollinen keskussairaala Recruiting
Helsinki, Finland, 00029
Contact: Sirpa Leppa, MD    +358504270820   
Principal Investigator: Sirpa Leppa, MD         
Tampereen yliopistollinen sairaala Recruiting
Tampere, Finland, 33520
Contact: Marjukka Pollari, MD    +3583311611   
Principal Investigator: Marjukka Pollari, MD         
Ospedale San Raffaele Recruiting
Milan, Milano, Italy, 20132
Contact: Daniela DeLorenzo   
Principal Investigator: Andres Ferreri, MD         
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII) Recruiting
Bergamo, Italy, 24127
Contact: Giuseppe Gritti, MD    390352673684   
Principal Investigator: Giuseppe Gritti, MD         
KO-MED Centra Kliniczne Recruiting
Biała Podlaska, Poland
Contact: Dominika Chwedoruk   
Principal Investigator: Piotr Centkowski, MD         
Uniwersyteckie Centrum Kliniczne Recruiting
Gdańsk, Poland
Contact: Michal Taszner   
Principal Investigator: Michal Taszner, MD         
BioResearch Group Sp. Z. o. o. Recruiting
Kajetany, Poland
Contact: Marta Marek   
Principal Investigator: Katarzyna Jarus-Dziedzic, MD         
Nasz Lekarz Przychodnie Medyczne Recruiting
Toruń, Poland
Contact: Judyta Rudzinska   
Principal Investigator: Dominik Chraniuk         
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego Recruiting
Wrocław, Poland, 50566
Contact: Tomasz Wrobel, MD    48717842754   
Principal Investigator: Tomasz Wrobel, MD         
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Mafalda Rodrigues   
Principal Investigator: Pau Abrisqueta, MD         
Institut Català d'Oncologia Recruiting
Barcelona, Spain
Contact: Anna Valer Serra         
Principal Investigator: Eva Gonzalez Barca, MD         
Fundacion Jimenez Diaz Recruiting
Madrid, Spain
Contact: Adriana Armellini   
Principal Investigator: Raul Cordoba, MD         
Sponsors and Collaborators
Hutchison Medipharma Limited
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Study Director: Vijay Jayaprakash, MD Hutchison Medipharma Limited
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Responsible Party: Hutchison Medipharma Limited Identifier: NCT03779113    
Other Study ID Numbers: 2018-523-00US1
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: January 11, 2022
Last Verified: December 2021
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:
mantle cell lymphoma
marginal zone lymphoma
waldenstrom macroglobulinemia
chronic lymphocytic leukemia
small lymphocytic lymphoma
small lymphocytic lymphoma post-BTK exposure
peripheral t-cell lymphoma
cutaneous B-cell lymphoma
Hodgkin lymphoma
follicular lymphoma
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases