Clinical trial NCT03588598: Safety, Tolerability, and Pharmacokinetics of SHC014748M in Patients With Indolent B-Cell Hematologic Malignancies
Official title: A Phase I Dose Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of SHC014748M in Patients With Relapsed or Refractory Indolent B-Cell Hematologic Malignancies.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
B-Cell Non-Hodgkin Lymphomas(NHL)
Keywords: CLL
SLL
NHL
SHC014748M
Phosphatidylinositol 3-kinase (PI3K)
Lead sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-07-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is a phase I, sequential dose escalation followed by cohort expansion study of SHC014748M, an oral inhibitor of PI3K delta, in patients with relapsed or refractory indolent B-cell hematologic malignancies.

Eligibility criteria: Inclusion Criteria:

1.18- 75 years of age.

2.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.

3.Patients have received at least 1 prior regimen (at least 2 cycles).

4.Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.

5.Life expectancy ≥ 3 months.

6.Patients have at least 1 measurable lesion that measures ≥1.5 cm in a single dimension as assessed by CT or MRI.

7.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；

8.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.

9.Subjects did not participate in other clinical trials within 3 months prior to study entry.

Exclusion Criteria:

1. Disease progression after previous treatment with any PI3Kδ inhibitors.
2. Had any other anti-tumor treatment within 4 weeks prior to screening (including radiotherapy, chemotherapy, hormone therapy, surgery or targeted therapy).
3. Evidence of central nervous system involvement of the malignancy.
4. 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.
5. 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.
6. Require any concomitant medication known to prolong the QT interval during the study.
7. Evidence of active bacterial, fungal, or viral infection.
8. 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).
9. Use of high-dose glucocorticoids (eg, ≥20 mg/day prednisone) or other immunosuppressants within 4 weeks prior to study entry.
10. Concomitant use of any strong inhibitors or inducers of CYP3A4.
11. Use of G-CSF or blood transfusion within 7 days before the hematology test at screening.
12. Prior autologous hematopoietic stem cell transplantation within 6 months prior to treatment initiation.
13. History of prior allogeneic hematopoietic stem cell transplantation.
14. Major surgery within 4 weeks prior to treatment initiation.
15. 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.
16. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the drug or previous significant bowel resection that would preclude adequate absorption of the study drug.
17. History of hypersensitivity to drugs similar to the study drug or inactive excipients of the study drug.
18. Women who are breastfeeding.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: 1 month
measure: Time to Peak Plasma Concentration（Tmax）
timeFrame: 1 month
measure: Peak Plasma Concentration (Cmax)
timeFrame: 1 month
measure: Half-life Time(t1/2)
timeFrame: 1 month
measure: Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: 1 month
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 12 months
measure: Lymph Node Response (LNR)
timeFrame: up to 12 months
measure: Time to Response (TTR)
timeFrame: up to 12 months
measure: Progression-Free Survival (PFS)
timeFrame: up to 12 months
measure: Duration of Response (DOR)
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jianyong Li, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital, Zhejiang University
name: Jie Jin, MD
role: PRINCIPAL_INVESTIGATOR
References: