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

Primary Purpose

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

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SHC014748M
Sponsored by
Nanjing Sanhome Pharmaceutical, Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring CLL, SLL, NHL, SHC014748M, Phosphatidylinositol 3-kinase (PI3K)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital with Nanjing Medical UniversityRecruiting
  • The First Affiliated Hospital, Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SHC014748M treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Dose Limiting Toxicity (DLT)
Time to Peak Plasma Concentration(Tmax)
Peak Plasma Concentration (Cmax)
Half-life Time(t1/2)
Area Under the Plasma Concentration Versus Time Curve (AUC)

Secondary Outcome Measures

Objective Response Rate (ORR)
Lymph Node Response (LNR)
Time to Response (TTR)
Progression-Free Survival (PFS)
Duration of Response (DOR)

Full Information

First Posted
June 28, 2018
Last Updated
April 27, 2019
Sponsor
Nanjing Sanhome Pharmaceutical, Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03588598
Brief Title
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

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 7, 2018 (Actual)
Primary Completion Date
July 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanjing Sanhome Pharmaceutical, Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), B-Cell Non-Hodgkin Lymphomas(NHL)
Keywords
CLL, SLL, NHL, SHC014748M, Phosphatidylinositol 3-kinase (PI3K)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SHC014748M treatment
Arm Type
Experimental
Arm Description
SHC014748M capsule, 50, 100, 150, 200, 250 mg, QD, 28 days for each cycle
Intervention Type
Drug
Intervention Name(s)
SHC014748M
Intervention Description
a selective PI3Kδ inhibitor
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT)
Time Frame
1 month
Title
Time to Peak Plasma Concentration(Tmax)
Time Frame
1 month
Title
Peak Plasma Concentration (Cmax)
Time Frame
1 month
Title
Half-life Time(t1/2)
Time Frame
1 month
Title
Area Under the Plasma Concentration Versus Time Curve (AUC)
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Time Frame
up to 12 months
Title
Lymph Node Response (LNR)
Time Frame
up to 12 months
Title
Time to Response (TTR)
Time Frame
up to 12 months
Title
Progression-Free Survival (PFS)
Time Frame
up to 12 months
Title
Duration of Response (DOR)
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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: 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. 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. History of hypersensitivity to drugs similar to the study drug or inactive excipients of the study drug. Women who are breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Guo
Phone
+86025-81066427
Email
guoweiyf@sanhome.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaodan Lyu
Phone
+86025-81066469
Email
lvxd@sanhome.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianyong Li, MD
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jie Jin, MD
Organizational Affiliation
The First Affiliated Hospital, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital with Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianyong Li, MD
Facility Name
The First Affiliated Hospital, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jin, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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