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

NCT03128164 | Completed Phase 1

• 1 other identifier: 2016-689-GLOB1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 3

Brief 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 consists of a dose escalation stage (Stage I) and a dose expansion stage (Stage II).

Conditions

Lymphomas

Outcome Measures

Primary Outcomes (2)

• Dose limited toxicities evaluated with NCI CTCAE v4.03

  Incidence of dose limited toxicities and associated dose of HMPL-689

  within 28 days after the first dose

• Objective response rate (ORR)

  Overall response rate (ORR) is defined as the proportion of patients who have a CR or PR

  Through study completion, 1 year after the last patient has enrolled in the study or all patients have discontinued the study, whichever comes sooner

Secondary Outcomes (2)

• Maximum plasma concentration calculated with Blood samples

  within 29 days after the first dose

• Time to reach maximum concentration calculated with Blood samples

  within 29 days after the first dose

Other Outcomes (6)

• Adverse events evaluated by NCI CTCAE v4.03

  from the first dose to within 30 days after the last dose

• Complete response rate (CR rate)

  Through study completion, 1 year after the last patient has enrolled in the study or all patients have discontinued the study, whichever comes sooner

• Time to response (TTR)

  Through study completion, 1 year after the last patient has enrolled in the study or all patients have discontinued the study, whichever comes sooner

Study Arms (1)

Six arm including in dose expansion stage by following:

EXPERIMENTAL

* Arm A: patients with MZL (subtype including nodal, extra-nodal and splenic) who received ≥ 1 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm B: patients with CLL/SLL who received ≥ 1 previous line of systematic treatment and at least one of which included purine-based regimen or CD20-directed regimen * Arm C: patients with FL (grade 1, 2, and 3a) who received ≥ 2 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm D: patients with MCL who received ≥ 2 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm E: patients with DLBCL (including GCB and non-GCB, Richter' transformation) who received ≥ 2 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm F: patients with PTCL who received ≥ 2 previous line of systematic treatment

Drug: HMPL-689

Interventions

HMPL-689 DRUG

Two strengths of HMPL-689 capsules (2.5 mg and 10 mg) will be used for clinical studies. The drug products are capsules.

Six arm including in dose expansion stage by following:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF)
• Ability to comply with the protocol
• Age ≥ 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically confirmed lymphoma
• Relapsed or refractory disease after failed of standard of care or no standard of care existed according to local guideline, and need further systematic treatment in the opinion of the investigator
• At least 1 bi-dimensionally measurable nodal disease, defined as \>1.5 cm (extra-nodal lesion\>1.0 cm ) in its largest dimension by computerized tomography (CT) scan is required for patients with lymphoma other than CLL; lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by magnetic resonance image (MRI) instead
• Expected survival of more than 24 weeks
• Female patients of child-bearing potential and male patients with partners 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 30 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

You may not qualify if:

• Patients with CNS(Central nervous system) involvement
• Any of the following laboratory abnormalities:
• Absolute neutrophil count \< 1.5×109/L Hemoglobin \<90 g/L Platelets\< 100 ×109/L
• 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 (Ccr) (i.e., estimated Glomerular Filtration Rate, \[eGFR\[ according to the method of Cockcroft-Gault )\< 60 mL/min
• 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
• Serum amylase or lipase \>ULN at screening
• 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
• 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)
• Prior treatment with any PI3K inhibitors and discontinued due to disease progression

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (3)

TongJi Medical College Huazhong University of Science& Technology

Wuhan, Hubei, 430030, China

Location

Sun Yat-sen University cancer center

Guangzhou, 510060, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Junning Cao, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study consists of a dose escalation stage (Stage I) and a dose expansion stage (Stage II). Dose escalation will be performed according to a modified toxicity probability interval scheme-2 (mTPI-2). Expansion stage of the study enrolled 143 patients with B cell lymphoma, including CLL/SLL, FL, MZL, DLBCL, MCL and PTCL, Patients were treated with RP2D as starting dose.

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 25, 2017
• Study Start: August 8, 2017
• Primary Completion: August 2, 2023
• Study Completion: August 2, 2023
• Last Updated: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)