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

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ClinicalTrials.gov Identifier: NCT03786926
Recruitment Status : Active, not recruiting
First Posted : December 26, 2018
Last Update Posted : January 13, 2023
Sponsor:
Information provided by (Responsible Party):
Hutchmed

Study Description
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Brief 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

Condition or disease Intervention/treatment Phase
Lymphoma Drug: HMPL-689 Phase 1

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Relapsed or Refractory Lymphoma
Actual Study Start Date : August 26, 2019
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment
All patients take HMPL-689 taken daily
 Drug: HMPL-689
HMPL-689 is a PI3Kδ inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. Number of adverse events as evaluated by the NCI CTCAE v5.0 grade [ Time Frame: From first dose to within 30 days after last dose ]
    The safety and tolerability of HMPL-689 dose will be evaluated based on adverse events data


Secondary Outcome Measures :
  1. maximum plasma concentration (Cmax) [ Time Frame: from cycle 1 day 1 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days) ]
    To characterize the pharmacokinetic (PK) properties of HMPL-689 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 30 min pre-dose until cycle 2 day 1 30 min pre dose (escalation) from cycle 1 day 1 30 min pre-dose to Cycle 5 day 1 pre-dose 30 min (expansion) (cycle is 28 days) ]
    To characterize the pharmacokinetic (PK) properties of HMPL-689 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 of last dose ]
    To evaluate the anti-tumor activity of HMPL-689 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


Eligibility Criteria
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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
Criteria

Inclusion Criteria:

  1. (ECOG) performance status of 0 or 1;
  2. Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);

  3. 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);
  4. Expected survival of more than 24 weeks.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from study entry:

  1. 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);
    • 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;
  4. International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin time (aPTT) > 1.5 × ULN;
  5. Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN;
  6. Patients with presence of second primary malignant tumors within the last 2 years;
  7. Clinically significant history of liver disease;
  8. Prior treatment with any PI3Kδ inhibitors;
  9. 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;
  10. Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis);
  11. Major surgical procedure within 4 weeks prior to initiation of study treatment;
  12. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia;
  13. New York Heart Association (NYHA) Class II or greater congestive heart failure;
  14. Congenital long QT syndrome or QTc >470 msec;
  15. Currently use medication known to cause QT prolongation or torsades de pointes;
  16. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment;
  17. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment;
  18. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease;
  19. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);
  20. Patients with ongoing chronic gastrointestinal diseases;
  21. 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.
Contacts and Locations
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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): NCT03786926


Locations
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Sponsors and Collaborators
Hutchmed
Investigators
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Study Director: Vijay Jayaprakash, MD Hutchison Medipharma Limited
Principal Investigator: Nilanjan Ghosh, MD Atrium Health Levine Cancer Institute
Principal Investigator: Jonathan B Cohen, MD Emory Winship Cancer Institute
More Information
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Responsible Party: Hutchmed
ClinicalTrials.gov Identifier: NCT03786926    
Other Study ID Numbers: 2018-689-00US1
First Posted: December 26, 2018    Key Record Dates
Last Update Posted: January 13, 2023
Last Verified: January 2023
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 Hutchmed:
CLL
SLL
FL
MZL
LPL
 WM
MCL
PTCL
CBCL
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases