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

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.

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); B-Cell Non-Hodgkin Lymphomas(NHL)
• Intervention / Treatment: Drug: SHC014748M

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei Guo; Phone Number: +86025-81066427; Email: guoweiyf@sanhome.com
• Study Contact Backup: Name: Xiaodan Lyu; Phone Number: +86025-81066469; Email: lvxd@sanhome.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Jianyong Li, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University
      • Contact: Jie Jin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHC014748M treatment; SHC014748M capsule， 50, 100, 150, 200, 250 mg, QD, 28 days for each cycle	Drug: SHC014748M; a selective PI3Kδ inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS)	up to 12 months
Objective Response Rate (ORR)	up to 12 months
Lymph Node Response (LNR)	up to 12 months
Time to Response (TTR)	up to 12 months
Duration of Response (DOR)	up to 12 months

Collaborators and Investigators

• Sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.
• Investigators: Principal Investigator: Jianyong Li, MD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2018
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 27, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: NHL; CLL; SLL; SHC014748M; Phosphatidylinositol 3-kinase (PI3K)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma; Lymphoma, B-Cell; Hematologic Neoplasms; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: SHC014-I-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No