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A Study of HMPL-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms

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ClinicalTrials.gov Identifier: NCT02857998
Recruitment Status : Recruiting
First Posted : August 5, 2016
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Brief Summary:
A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms

Condition or disease Intervention/treatment Phase
Mature B-cell Neoplasms Drug: HMPL-523 Phase 1

Detailed Description:

There are two stages in this study: a dose-escalation stage (stage 1) and a dose-expansion stage (stage 2).

Dose-escalation stage (stage 1):

The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and maximum tolerated dosage determination. Approximately 27 to 42 dose limited toxicities evaluable patients will be enrolled. The actual number of patients depends on the dose limited toxicities situation as well as the maximum tolerated dosage reached at this stage.

Dosing will begin at 200mg once daily. A cycle of study treatment will be defined as 28 days of continuous dosing.

Dose-expansion stage (stage 2):

This phase is to further evaluate the safety, the pharmacokinetics and anti-tumor activity of HMPL-523 at recommended phase 2 dosage in approximately 190 patients with relapsed or refractory Hematologic Malignancies.

In this stage, approximately 190 patients with Mature B-cell Neoplasms will be enrolled with recommended phase 2 dosage 600mgQD as starting dosing. The tumor types of the expansion stage are restricted to Chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), Mantle cell lymphoma (MCL), Follicular Lymphoma (FL), Diffuse large B-cell lymphoma (DLBCL), Marginal zone lymphoma (MZL)and Waldenstrom's macroglobulinemia (WM)/Lymphoplasmacytic lymphoma(LPL) Subjects will receive HMPL-523 with every 28-day treatment cycle until disease progression, death, or intolerable toxicity, whichever comes first.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 217 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms
Actual Study Start Date : December 27, 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HMPL-523
Oral administration, at dose of 200, 400, 600 and 800 mg once daily;at dose of 200,300, 400mg twice daily at Dose-escalation stage; At Dose-expansion stage, if patients dosing at 600mgQD.
Drug: HMPL-523
Oral administration, once daily
Other Name: HMPL-523 Acetate




Primary Outcome Measures :
  1. Dose limited toxicities evaluated with NCI CTCAE v4.03 [ Time Frame: within 28 days after the first dose ]
    Incidence of dose limited toxicities and associated dose of HMPL-523


Secondary Outcome Measures :
  1. Maximum plasma concentration calculated with Blood samples [ Time Frame: within 29 days after the first dose ]
    Blood samples will be taken to measure the levels of study drug

  2. Time to reach maximum concentration calculated with Blood samples [ Time Frame: within 29 days after the first dose ]
    Blood samples will be taken to measure the levels of study drug

  3. Objective response rate [ Time Frame: within 30 days after the last dose ]
    the proportion of subjects who have a Complete Response or Partial Response

  4. Adverse events evaluated by NCI CTCAE v4.03 [ Time Frame: from the first dose to within 30 days after the last dose ]
    Incidence of adverse events and associated dose of HMPL-523



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. Signed Informed Consent Form
  2. Age >=18 years
  3. Histologically relapsed or refractory mature B-cell Neoplasms, have failed at least one prior therapy or patients who are unable to tolerate standard therapy or no curative therapy or therapy of higher priority exists
  4. ECOG performance status of 0 or 1
  5. Expected survival of more than 24 weeks as determined by the investigator
  6. In expansion stage, Subjects should have at least one dual diameter measurable lesion expect for subject with CLL or subject with LPL/WM with abonormal immunoglobulin

Exclusion Criteria:

  1. Patients with primary CNS lymphoma
  2. Any of the following laboratory abnormalities:

    • Absolute neutrophil count<1.5×109/L
    • Hemoglobin <80g/L
    • Platelet<75 ×109 /L
  3. Inadequate organ function, defined by the following:

    • Total bilirubin >1.5the ULN with the following exception:

      • Patients with known Gilbert disease who have serum bilirubin level ≤3 the ULN and normal AST/ALT may be enrolled.
  4. AST and/or ALT > 2.5 the ULN with the following exception:Patients with documented disease infiltration of the liver may have AST and/or ALT levels ≤ 5 the ULN.
  5. Serum amylase or lipase > the ULN
  6. Serum creatinine > 1.5 the ULN or estimated creatinine clearance < 50 mL/min
  7. International normalized ratio (INR)>1.5 the ULN or activated partial thromboplastin time (aPTT)>1.5 the ULN
  8. Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
  9. Pregnant (positive pregnancy test) or lactating women
  10. New York Heart Association (NYHA) Class II or greater congestive heart failure
  11. Congenital long QT syndrome or QTc > 480 msec
  12. Currently use medication known to cause QT prolongation.
  13. Subjects with presence of 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).
  14. Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, or radiotherapy within 3 weeks prior to initiation of study treatment
  15. Herbal therapy ≤1 week prior to initiation of study treatment
  16. Prior treatment with any SYK inhibitors (Fostamatinib)
  17. Prior allogeneic stem cell transplant within 6 months prior to initiation of study treatment or with any evidence of active graft versus host disease or requirement for immunosuppressants within 28 days prior to initiation of study treatment
  18. Clinically significant active infection (pneumonia)
  19. Major surgical procedure within 4 weeks prior to initiation of study treatment
  20. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment
  21. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
  22. Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤1, except for alopecia

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): NCT02857998


Locations
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China, Beijing
BeijingCancer Hospital Recruiting
Beijing, Beijing, China
Contact: Jun Zhu    862188196596      
Principal Investigator: Lin Shen, MD.PHD         
China
Fudan University Shanghai Cancer Hospital Recruiting
Shanghai, China, 200032
Contact: Junning Cao    8613651680209      
Sponsors and Collaborators
Hutchison Medipharma Limited

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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT02857998     History of Changes
Other Study ID Numbers: 2015-523-00CH1
First Posted: August 5, 2016    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases