Safety, Tolerability, and Pharmacokinetics of SHC014748M in Patients With Indolent B-Cell Hematologic Malignancies

NCT03588598 | Unknown Phase 1

• 1 other identifier: SHC014-I-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of SHC014748M in patients with relapsed or refractory indolent B-cell hematologic malignancies.

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); B-Cell Non-Hodgkin Lymphomas(NHL)

Keywords

CLL; SLL; NHL; SHC014748M; Phosphatidylinositol 3-kinase (PI3K)

Outcome Measures

Primary Outcomes (5)

• Dose Limiting Toxicity (DLT)

  1 month

• Time to Peak Plasma Concentration（Tmax）

  1 month

• Peak Plasma Concentration (Cmax)

  1 month

• Half-life Time(t1/2)

  1 month

• Area Under the Plasma Concentration Versus Time Curve (AUC)

  1 month

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  up to 12 months

• Lymph Node Response (LNR)

  up to 12 months

• Time to Response (TTR)

  up to 12 months

• Progression-Free Survival (PFS)

  up to 12 months

• Duration of Response (DOR)

  up to 12 months

Study Arms (1)

SHC014748M treatment

EXPERIMENTAL

SHC014748M capsule， 50, 100, 150, 200, 250 mg, QD, 28 days for each cycle

Drug: SHC014748M

Interventions

SHC014748M DRUG

a selective PI3Kδ inhibitor

SHC014748M treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age.
• Histologically or cytologically confirmed diagnosis of relapsed or refractory indolent B-cell hematologic malignancies, including but not limited to CLL / SLL, FL (grade 1, 2 or 3a), or MZL.
• Patients have received at least 1 prior regimen (at least 2 cycles).
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
• Life expectancy ≥ 3 months.
• Patients have at least 1 measurable lesion that measures ≥1.5 cm in a single dimension as assessed by CT or MRI.
• Adequate organ function, as defined by the following values: ANC≥1.0×10\^9/L； PLT≥50×10\^9/L； Hb≥80 g/L； TBIL≤1.5×ULN； ALT and AST≤2.5×ULN； BUN and Cr≤1.5×ULN； LVEF≥50%； QTcF \<450 ms for male, QTcF \<470 ms for female；
• Men and women of childbearing potential are willing to employ an effective method of contraception for the entire duration of study and 6 months after the last dose, and female subjects of childbearing potential have a negative pregnancy test at baseline.
• Subjects did not participate in other clinical trials within 3 months prior to study entry.

You may not qualify if:

• Disease progression after previous treatment with any PI3Kδ inhibitors.
• Had any other anti-tumor treatment within 4 weeks prior to screening (including radiotherapy, chemotherapy, hormone therapy, surgery or targeted therapy).
• Evidence of central nervous system involvement of the malignancy.
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, uncontrolled pleural effusion and ascites, uncontrolled diabetes, non-infectious pneumonia, and any other severe cardiovascular, respiratory, nervous and mental diseases.
• Any of the severe heart diseases, including New York Heart Association (NYHA) Class II or greater heart failure, arrhythmias requiring medical treatment, and history of myocardial infarction or unstable angina within 6 months prior to screening.
• Require any concomitant medication known to prolong the QT interval during the study.
• Evidence of active bacterial, fungal, or viral infection.
• Active infection with hepatitis B virus (HBV) (HBsAg positive, or HBsAg negative and HBV-DNA positive), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Use of high-dose glucocorticoids (eg, ≥20 mg/day prednisone) or other immunosuppressants within 4 weeks prior to study entry.
• Concomitant use of any strong inhibitors or inducers of CYP3A4.
• Use of G-CSF or blood transfusion within 7 days before the hematology test at screening.
• Prior autologous hematopoietic stem cell transplantation within 6 months prior to treatment initiation.
• History of prior allogeneic hematopoietic stem cell transplantation.
• Major surgery within 4 weeks prior to treatment initiation.
• History of a non-lymphoma malignancy in the past five years except for the following: adequately treated cervical carcinoma in situ, local basal cell or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Nanjing Sanhome Pharmaceutical, Co., Ltd.: lead

Study Sites (2)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jianyong Li, MD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

• Jie Jin, MD

  The First Affiliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Guo

CONTACT

+86025-81066427; guoweiyf@sanhome.com

Xiaodan Lyu

CONTACT

+86025-81066469; lvxd@sanhome.com

Study Design

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

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: July 17, 2018
• Study Start: September 7, 2018
• Primary Completion: July 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 30, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)