Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

  • STATUS
    Recruiting
  • End date
    Aug 31, 2023
  • participants needed
    270
  • sponsor
    Hutchison Medipharma Limited
Updated on 22 December 2021
lymphoma

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

Description

This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients with relapsed or refractory lymphoma.

HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling pathway

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.

Details
Condition Lymphoma
Treatment HMPL-689
Clinical Study IdentifierNCT03786926
SponsorHutchison Medipharma Limited
Last Modified on22 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

(ECOG) performance status of 0 or 1
Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL)
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)
Expected survival of more than 24 weeks

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study
entry
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)
AST or ALT > 2.5 × ULN
Estimated creatinine clearance (CrCl) per Cockcroft-Gault
Dose Escalation stage of trial (Stage 1) - CrCl < 40 mL/min
Dose Expansion stage of trial (Stage 2) - CrCl <30 mL/min
International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin
Clinically significant history of liver disease
time (aPTT) > 1.5 × ULN
Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN
Any prior use of the following: cancer 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, any use of strong CYP3A4 inducers within 2 weeks prior to initiation of study treatment, prior autologous transplant within 6 months of study treatment, prior allogenic stem cell transplant within 6 months of study treatment
Patients with presence of second primary malignant tumors within the last 2 years
Major surgical procedure within 4 weeks prior to initiation of study treatment
Prior treatment with any PI3Kδ inhibitors
Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia
Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis)
New York Heart Association (NYHA) Class II or greater congestive heart failure
Congenital long QT syndrome or QTc >470 msec
Currently use medication known to cause QT prolongation or torsades de pointes
History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment
History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment
Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
Patients with ongoing chronic gastrointestinal diseases
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 or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
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