Clinical trial NCT04500561: YY-20394 、GEMOX Treatment Diffuse Large B-cell Lymphoma Single Arm, Open, Multicentrized Phase 1b/2 Clinical Trial
Official title: YY-20394 Combined With GEMOX in the Treatment of Patients With Relapsed and/or Refractory Diffuse Large B-cell Lymphoma With a Single Arm, Open, Multicentrized Phase 1b/2 Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Lead sponsor: Shanghai YingLi Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2020-08-05
Enrollment: 28
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
Intervention model description: YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of GEMOX was treated according to clinical standards
Primary purpose: TREATMENT

Brief summary: This study is a one-arm, open, multicenter phase 1b/2 clinical trial of YY-20394 combined with GEMOX second-line or above in patients with relapsed and/or refractory diffuse large B-cell lymphoma.

YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of GEMOX was treated according to clinical standards.

Detailed description: This study is a one-arm, open, multicenter phase 1b/2 clinical trial of YY-20394 combined with GEMOX second-line or above in patients with relapsed and/or refractory diffuse large B-cell lymphoma.

YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of GEMOX was treated according to clinical standards.

The first six subjects of group to evaluate the safety of YY - 20394 joint GEMOX, if the joint treatment of 6 cases of subjects before, If YY-20394 and/or chemotherapy related 4 degrees of hematology toxicity or level 3 non hematologic toxicity were appearanced less than 2 cases, continued to dose of 80 mg/day, if more than 2 cases, YY-20394 doses dropped to 60 mg/day.

Eligibility criteria: Inclusion Criteria:

- Patients with recurrent and/or refractory diffuse large B-cell lymphoma confirmed histologically or cytologically; Progress after first-line or above systemic treatment (at least CD20 monoclonal antibody treatment); ECOG Performance Status (PS) grade 0 \~ 1; Expected survival ≥3 months; The patient has at least one measurable lesion conforming to the IWG2007 standard; Good organ function level:ANC≥1.0×109/L；PLT≥70×109/L；Hb≥80 g/L

;TBIL≤1.5×ULN； ALT和AST≤2.5×ULN；BUN/Urea和Cr≤1.5×ULN；LVEF≥50%； The Fridericia method corrected the QT interval (QTcF) for males \< 450 ms and females \< 470 ms.

From the end of any previous anti-tumor therapy (including radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy) to the washout period of this study ≥4 weeks; Did not participate in the clinical trial as a subject within 1 month before the trial; According to the researcher's judgment, it can comply with the experimental protocol; Volunteer to participate in this clinical trial, understand the study procedures and be able to sign the informed consent in person.

Exclusion Criteria:

* Those who have used PI3K as the target of anti-tumor drug progression (except those who cannot tolerate out of the group); Any other anti-tumor therapy within 4 weeks; The presence of a third interstitial effusion that cannot be controlled by drainage or other methods (such as massive pleural and ascites); Use of steroid hormone dosage (equivalent amount of prednisone) greater than 20mg/ day within 4 weeks, and continuous use for more than 14 days; Unable to swallow, chronic diarrhea and intestinal obstruction, existing multiple factors affecting drug intake and absorption; Unable to suspend medications that may prolong QT interval during the study (e.g., antiarrhythmic agents); Having lympoma with central nervous system (CNS) invasion; Allergic constitution, or known anaphylaxis to any component of this product; Having active viral, bacterial or fungal infection requiring treatment (e.g., pneumonia); Uncontrolled diabetes, pulmonary fibrosis, acute pulmonary disease, interstitial lung disease, or liver failure; Patients with HBV, HCV infection (defined as HbsAg and/or HbcAb positive and HBV DNA copy number ≥1×104 copy number /ml or ≥2000 IU/ml) or acute or chronic active hepatitis C; Medical history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency disease, or history of organ transplantation or allogeneic bone marrow transplantation; Having received autologous hematopoietic stem cell transplantation within 90 days prior to the first dose in this study; Any cardiac disease, including (1) angina pectoris; (2) arrhythmia requiring drug therapy or of clinical significance; (3) myocardial infarction; (4) heart failure; (5) any other cardiac disease that is judged by investigators as not suitable to participate in this trial; Pregnant or lactating women or baseline pregnancy testing positive for fertile women; Concomitant diseases (such as serious hypertension, diabetes mellitus, thyroid disease) seriously hazardous to patient's safety or completion of study as judged by the investigator; Having other primary malignancy in recent 5 years;

Primary outcomes:
measure: objective remission rate
timeFrame: with in 42 days after the first dos
Secondary outcomes:
measure: disease control rate
timeFrame: with in 42 days after the first dos
measure: Progression Free Survival
timeFrame: with in 42 days after the first dos
measure: drug safety
timeFrame: one and half a year
Other outcomes:
Locations:
Study officials:
affiliation: Cancer Prevention center affiliated to Sun Yat-sen University
name: Zhiming Li, PHD
role: PRINCIPAL_INVESTIGATOR
References: