An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma
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|ClinicalTrials.gov Identifier: NCT03779113|
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : February 23, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Non Hodgkin Lymphoma||Drug: HMPL-523||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||December 2024|
|Estimated Study Completion Date :||January 2026|
All patients to received study drug (HMPL-523)
- 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.
- 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
- 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
- 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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Patients must meet the following criteria to be eligible for study entry:
- Signed informed consent form (ICF).
- Age ≥18 years.
- ECOG performance status of 0 or 1.
- 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
- Patients with relapsed or refractory lymphoma who have exhausted all approved therapy options.
- In the dose expansion stage, patients must have measurable disease for an objective response assessment, except for patients with CLL and WM/LPL
- 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
- Expected survival of more than 24 weeks as determined by the investigator.
- 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.
- Patients with primary central nervous system (CNS) lymphoma.
- Any of the following laboratory abnormalities: Absolute neutrophil count<1.0×10^9/L, Hemoglobin <80 g/L, Platelets <50×10^9/L
- 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
- 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).
- Any anticancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine, or radiotherapy within 3 weeks prior to the initiation of study treatment.
- Herbal therapy within 1 week prior to the initiation of study treatment.
- Prior use of any anti-cancer vaccine
- Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)
- Prior administration of radioimmunotherapy within 3 months before initiation of study treatment.
- 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
- Adverse events from prior anticancer therapy that have not resolved to Grade ≤1, except for alopecia.
- Prior autologous stem cell transplant within 6 months prior to the initiation of study treatment.
- 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.
- Clinically significant active infection (eg, pneumonia).
- Major surgical procedure within 4 weeks prior to the initiation of study treatment.
- 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.
- Pregnant (positive serum beta human chorionic gonadotropin test) or lactating women.
- New York Heart Association Class II or greater congestive heart failure.
- Congenital long QT syndrome or correct QT interval using Fridericia's formula (QTcF) >480 msec
- Current use of medication known to cause QT prolongation or Torsades de Pointes
- History of myocardial infarction or unstable angina within 6 months prior to the initiation of study treatment.
- History of stroke or transient ischemic attack within 6 months prior to the initiation of study treatment.
- Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease.
- Treatment in a clinical study within 30 days prior to the initiation of study treatment.
- 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.
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): NCT03779113
|Contact: Vijay Jayaprakash, MDfirstname.lastname@example.org|
|Contact: Rathi Pillai, MDemail@example.com|
|Study Director:||Vijay Jayaprakash, MD||Hutchmed|
|Other Study ID Numbers:||
|First Posted:||December 19, 2018 Key Record Dates|
|Last Update Posted:||February 23, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
chronic lymphocytic leukemia
Neoplasms by Histologic Type
Immune System Diseases