Clinical trial NCT04431089: Efficacy and Safety of SHC014748M in Patients With Relapsed or Refractory Follicular (FL) or Marginal Zone (MZL) Lymphoma
Official title: A Phase II Multicenter Study to Investigate the Efficacy and Safety of SHC014748M in Patients With Relapsed or Refractory Follicular (FL) or Marginal Zone (MZL) Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Follicular Lymphoma(FL)
Marginal Zone Lymphoma(MZL)
Keywords: FL
MZL
SHC014748M
Phosphatidylinositol 3-kinase (PI3K)
Lead sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-16
Enrollment: 122
Sex: ALL
Minimum age (years): 18
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 efficacy and safety of SHC014748M in patients with relapsed or refractory relapsed or refractory follicular (FL) or marginal one (MZL) lymphoma.

Detailed description: This is a phase II, multicenter study to assess the efficacy and safety of SHC014748M, an oral inhibitor of PI3K delta, in patients with relapsed or refractory relapsed or refractory follicular (FL) or marginal one (MZL) lymphoma.

Eligibility criteria: Inclusion Criteria:

* Adult, male and female volunteers, above 18 years of age inclusive.
* Histologically or cytologically confirmed diagnosis of relapsed or refractory FL(grade 1, 2 or 3a) and MZL, including splenic marginal zone lymphoma(SMZL), nodal marginal zone B cell lymphoma(NMZL) and mucosa associated lymphoid tissue(MALT) lymphoma. Relapse refers to disease progression after adequate treatment to remission；refractory refers to no remission after adequate treatment. The above "remission" includes complete remission and partial remission. Adequate treatment refers to two or more treatments with CD20 monoclonal antibody (CDE approved for marketing) combined with alkylation agent, including but not limited to bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan and nitrosoureas.
* 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≤2×ULN(TBIL\>2×ULN for subjects with Gilbert syndrome,TBIL\>3×ULN for subjects with focal compression of bile duct judged by investigators); ALT and AST≤2.5×ULN(ALT and AST≤5×ULN for subjects with impaired liver function caused by hepatic infiltration);blood urea nitrogen(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 1 month prior to study entry.
* Provision of signed and dated, written informed consent prior to any study-specific evaluation.

Exclusion Criteria:

* Previous treatment with any PI3Kδ inhibitors.
* Evidence of aggressive lymphoma(suspected clinical transformation should be conformed by biopsy).
* Had any other anti-tumor treatment within 4 weeks prior to screening(including radiotherapy, chemotherapy, Chinese herbal anti-tumor treatment and major surgery); targeted therapy with 5 half-life period prior to screening.
* 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, severe or debilitating lung disease.
* 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.Requiring any concomitant medication known to prolong the QT interval within 5 half-life period.
* Evidence of active bacterial, fungal, or viral infection, and need systemic treatment.
* 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).
* Concomitant use of any strong inhibitors or inducers of CYP3A4(except drug withdrawal prior to first dose of investigational drug.
* Use of granulocyte colony-stimulating factor(G-CSF) or blood transfusion within 7 days before the hematology test at screening.
* Prior autologous hematopoietic stem cell transplantation within 3 months prior to screening.
* History of immune deficiency(acquired and congenital), or history of organ transplantation, or allogeneic bone marrow or hematopoietic stem cell transplantation; with active autoimmune disease or history of autoimmune disease including Interstitial pneumonia, autoimmune enteritis, autoimmune hepatitis and systemic lupus erythematosus
* History of any uncured malignant tumor in the past five years except for the following: clinically cured cervical or breast carcinoma in situ, local basal cell or squamous cell carcinoma of the skin, thyroid tumor.
* Inability to swallow the drug, or history of diseases affecting gastrointestinal functions significantly including malabsorption syndrome,bariatric surgery,inflammatory bowel disease, partial or complete intestinal obstruction.
* Adverse events occurred during previous anticancer therapy have not been recovered to ≤1(CTCAE 5.0).
* History of hypersensitivity to the main composition or any inactive excipient of the study drug.
* Women who are breastfeeding.
* With alcohol or drug abuse disorder.
* History of stroke or intracranial hemorrhage with 6 months prior to screening.
* Attenuated live vaccination within 4 weeks prior to screening.
* With basic medical condition leading to risk of taking study drugs judged by investigators, or with confusion to toxicity and adverse events.
* Judgment by the investigator that the patient should not participate in the study.

Primary 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
measure: Mean Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Scale.
timeFrame: up to 12 months
Secondary outcomes:
measure: Safety and Tolerability of SHC014748M Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms.
timeFrame: up to 12 months
measure: Pharmacokinetics Parameter: Cmax
timeFrame: 4 weeks
measure: Pharmacokinetics Parameter: Tmax
timeFrame: 4 weeks
measure: Pharmacokinetics Parameter: ACUlast
timeFrame: 4 weeks
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
References: