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

Sponsor
Hutchison Medipharma Limited (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03786926
Collaborator
(none)
270
Enrollment
20
Locations
1
Arm
48.2
Anticipated Duration (Months)
13.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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
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

Study Type:
Interventional
Anticipated Enrollment :
270 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 :
Aug 26, 2019
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Aug 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment

All patients take HMPL-689 taken daily

Drug: HMPL-689
HMPL-689 is a PI3Kδ inhibitor

Outcome Measures

Primary Outcome Measures

  1. Number of adverse events as evaluated by the NCI CTCAE v5.0 grade [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) [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) [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 [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

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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);

  1. 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; <1.0×109/L, Hemoglobin <80 g/L Platelets <50 ×109/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;

  1. International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin time (aPTT) > 1.5 × ULN;

  2. Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN;

  3. Patients with presence of second primary malignant tumors within the last 2 years;

  4. Clinically significant history of liver disease;

  5. Prior treatment with any PI3Kδ inhibitors;

  6. 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;

  7. Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis);

  8. Major surgical procedure within 4 weeks prior to initiation of study treatment;

  9. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia;

  10. New York Heart Association (NYHA) Class II or greater congestive heart failure;

  11. Congenital long QT syndrome or QTc >470 msec;

  12. Currently use medication known to cause QT prolongation or torsades de pointes;

  13. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment;

  14. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment;

  15. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease;

  16. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);

  17. Patients with ongoing chronic gastrointestinal diseases;

  18. 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

Locations

Site City State Country Postal Code
1 Winship Cancer Institute of Emory University Atlanta Georgia United States 30322
2 Clinical Research Alliance, Inc Westbury New York United States 11590
3 Levine Cancer Institute- Atrium Health Charlotte North Carolina United States 28204
4 Baylor Scott and White Research Institute Dallas Texas United States 75246
5 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
6 Helsingin yliopistollinen keskussairaala Helsinki Finland 00029
7 Tampereen yliopistollinen sairaala Tampere Finland 33520
8 Hopital Henri Mondor Créteil Cedex Val De Marne France 94010
9 Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS Bologna Italy
10 Ospedale San Raffaele Milan Italy
11 KO-MED Centra Kliniczne Biała Podlaska Poland
12 Uniwersyteckie Centrum Kliniczne Gdańsk Poland
13 BioResearch Group Sp. Z. o. o. Kraków Poland
14 NASZ LEKARZ Osrodek Badan Klinicznych Toruń Poland
15 Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego Wroclaw Poland 50-566
16 ICO Badalona - Hospital Universitari Germans Trias i Pujol Barcelona Spain
17 ICO l'Hospitalet - Hospital Duran i Reynals Barcelona Spain
18 Fundacion Jimenez Diaz Madrid Spain
19 Hospital Universitario Virgen del Rocio Seville Spain
20 Hospital Universitario Virgen Macarena Seville Spain

Sponsors and Collaborators

  • Hutchison Medipharma Limited

Investigators

  • Study Director: Vijay Jayaprakash, MD, Hutchison Medipharma Limited
  • Principal Investigator: Nilanjan Ghosh, MD, Levine Cancer Institute
  • Principal Investigator: Jonathan B Cohen, MD, Emory Winship Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hutchison Medipharma Limited
ClinicalTrials.gov Identifier:
NCT03786926
Other Study ID Numbers:
  • 2018-689-00US1
First Posted:
Dec 26, 2018
Last Update Posted:
Feb 24, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Hutchison Medipharma Limited
CLL
SLL
FL
MZL
LPL
WM
MCL
PTCL
CBCL
Additional relevant MeSH terms:
Lymphoma

Study Results

No Results Posted as of Feb 24, 2022