A Study of HMPL-689 in Patients With Lymphomas Failed of Standard of Care or no Standard of Care Existed

• Status: Unknown status
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1, open-label study of HMPL-689 administered orally to patients with lymphoma for whom failed of standard care or have no standard of care.This study will consist of a dose escalation stage (Stage I) and a dose expansion stage (Stage II).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hutchison Medipharma Limited

Criteria

Inclusion Criteria:

1. Signed Informed Consent Form (ICF)

2. Ability to comply with the protocol

3. Age 18 and 75 years

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

5. Histologically confirmed lymphoma

6. Failed of standard of care or no standard of care existed according to local guideline

a. At least 1 bi-dimensionally measurable nodal disease, defined as >1.5 cm in its largest dimension by computerized tomography (CT) scan is required for patients with lymphoma other than CLL

7. In the dose expansion stage, patient recruitment will be restricted to the following lymphoma subtypes:

• B cell lymphoma, including CLL, SLL, FL, MZL,WM, DLBCL, burkitt lymphoma and MCL

8. Expected survival of more than 24 weeks

9. Male or female patients of child-bearing potential must agree to use double barrier contraception, condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), contraceptives (oral or parenteral), Implanon®, injectable or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from this criterion

Exclusion Criteria:

1. Patients with CNS(Central nervous system) involvement

2. Any of the following laboratory abnormalities:

• Absolute neutrophil count 1.5×109/L

• Hemoglobin< 80 g/L

• Platelets < 75 ×109/L

3. Inadequate organ function, defined by the following:

• Total bilirubin >1.5 x the upper limit of normal (ULN) with the following exception:

• Patients with known Gilbert's disease who have serum total and direct bilirubin level ≤ 2.5 x the ULN and normal aspartate transaminase (AST) and alanine transaminase (ALT) may be enrolled

• AST or ALT >2.5 x the ULN with the following exception:

• In the dose expansion stage: Patients with documented disease infiltration of the liver may have AST and ALT levels ≤ 5 x the ULN

• Serum creatinine >1.5 x the ULN or estimated creatinine clearance

4. International normalized ratio (INR) >1.5 x the ULN or activated partial thromboplastin time (aPTT) >1.5 x the ULN or Prothrombin Time (PT) >1.5 x the ULN

5. Patients with presence of second primary malignant tumors within the last 5 years, with the exception of the following non-invasive malignancies after curative treatment:

• Basal cell carcinoma of the skin

• Squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Carcinoma in situ of the breast

• Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for≥ 1 year prior to randomization

6. Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)

7. Prior treatment with any PI3Kδ inhibitors

• In stage II, patients discontinued PI3Kδ inhibitors for reasons other than disease progression are eligible

8. Any anti-cancer therapy, including chemotherapy, radiotherapy within 3 weeks prior to initiation of study treatment

9. G-CSF/blood transfusion is prohibited 7 days before the screening hematology test

10. Any steroid therapy or approved targeted small molecule agents for anti-neoplastic intent within 7 days or approximately 5 half-lives, whichever is the longer, prior to initiation of study treatment

11. Any monoclonal antibody for anti-neoplastic intent within 6 weeks or 2 half-lives, whichever is the longer, prior to initiation of study treatment

12. Prior use of any anti-cancer vaccine

13. Prior administration of radioimmunotherapy within 3 months prior to initiation of study treatment

14. Prior use of any drug that is a strong inducer of CYP3A4, strong inhibitor of CYP3A4 within 2 weeks prior to initiation of study treatment (refer to Appendix 13)

15. Prior autologous transplant within 6 months prior to initiation of study treatment

16. 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 21 days prior to initiation of study treatment

17. Clinically significant active infection (e.g., pneumonia)

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

19. Treatment within a clinical study of an investigational agent or using an investigational device within 30 days prior to initiation of study treatment

20. Adverse events from prior anti-cancer therapy that have not resolved to Grade 1, except for alopecia

21. Pregnant (positive pregnancy test) or lactating women

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

23. Congenital long QT syndrome or QTc > 450 msec

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

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

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

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

28. History of inflammatory bowel disease (e.g., Crohn disease or ulcerative colitis)

29. History of drug-induced pneumonitis

30. 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.