Mature B-cell NeoplasmsPhase 1NCT02857998
A Study of Hutchison MediPharma Limited(HMPL)-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms
A Phase 1 study testing HMPL-523 in people with Mature B-cell Neoplasms, run by Hutchison Medipharma Limited at 2 sites in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mature B-cell Neoplasms
- What is being tested?
- HMPL-523
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 2 sitesChina
- Study dates
- 27 Dec 2016to 30 Sep 2021
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form
- Age >=18 years
- 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
- Eastern Cooperative Oncology Group（ECOG） performance status of 0 or 1
- Expected survival of more than 24 weeks as determined by the investigator
- 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
Who cannot join
- Patients with primary central nervous system(CNS) lymphoma
- Any of the following laboratory abnormalities:
- Absolute neutrophil count<1.5×109/L
- Hemoglobin <80g/L
- Platelet<75 ×109 /L
- Inadequate organ function, defined by the following:
Show all 27Show fewer
- Total bilirubin >1.5the ULN with the following exception:
- Patients with known Gilbert disease who have serum bilirubin level ≤3 the upper limit of normal(ULN) and normal Aspartate aminotransferase(AST)/Alanine aminotransferase(ALT) may be enrolled.
- 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.
- Serum amylase or lipase > the ULN
- Serum creatinine > 1.5 the ULN or estimated creatinine clearance < 50 mL/min
- International normalized ratio (INR)>1.5 the ULN or activated partial thromboplastin time (aPTT)>1.5 the ULN
- 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)
- Pregnant (positive pregnancy test) or lactating women
- New York Heart Association (NYHA) Class II or greater congestive heart failure
- Congenital long QT syndrome or corrected QT interval (QTc) > 480 msec
- Currently use medication known to cause QT prolongation.
- 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).
- Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, or radiotherapy within 3 weeks prior to initiation of study treatment
- Herbal therapy ≤1 week prior to initiation of study treatment
- Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (Fostamatinib)
- 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
- Clinically significant active infection (pneumonia)
- Major surgical procedure within 4 weeks prior to initiation of study treatment
- History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment
- Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
- Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤1, except for alopecia
Trial locations and contacts
2 sites in 1 country.
China2 sites
BeijingCancer Hospital
Beijing, Beijing Municipality
Fudan University Shanghai Cancer Hospital
Shanghai, 200032
About this study
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
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
Read the 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 600milligram(mg) one a day(QD) 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.
- Conditions
- Mature B-cell Neoplasms
- Being tested
- HMPL-523
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-523Drug
Also called HMPL-523 Acetate
Oral administration, once daily
| Study group | Role | What they receive |
|---|---|---|
| HMPL-523 | Experimental | 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. Receives: Drug: HMPL-523 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limited toxicities evaluated with NCI CTCAE v4.03
Incidence of dose limited toxicities and associated dose of HMPL-523
Measured: within 28 days after the first dose
Secondary outcomes (4)
Maximum plasma concentration calculated with Blood samples
Blood samples will be taken to measure the levels of study drug
Measured: within 29 days after the first dose
Time to reach maximum concentration calculated with Blood samples
Blood samples will be taken to measure the levels of study drug
Measured: within 29 days after the first dose
Objective response rate
the proportion of subjects who have a Complete Response or Partial Response
Measured: within 30 days after the last dose
Adverse events evaluated by NCI CTCAE v4.03
Incidence of adverse events and associated dose of HMPL-523
Measured: from the first dose to within 30 days after the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2016 (estimated)
- Study start27 Dec 2016
- Primary completion30 Jun 2021
- Study completion30 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mature B-cell NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chen Yang, M.D., Study chair, Hutchison Medipharma Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02857998
- Sponsor's protocol ID
- 2015-523-00CH1
- Status last verified
- Jul 2024
- First submitted
- 3 Aug 2016
- Last updated
- 16 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Song Y, Cao J, Zhang Q, Li C, Qiu L, Qi J, Zhang H, Li W, Liu L, Jing H, Zhou K, Zhang W, Zhang L, Li D, Zou L, Yang H, Qian W, Zhou H, Hu J, Yin H, Fu S, Fan S, Xu Q, Wang J, Jia X, Dai G, Su W, Zhu J. Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors. Haematologica. 2024 Jul 1;109(7):2165-2176. doi: 10.3324/haematol.2022.282401.
PubMed 38235512