A Phase I Study of YY-20394 in Patients With B Cell Hematologic Malignancies

December 6, 2018 updated by: Shanghai YingLi Pharmaceutical Co. Ltd.

A Phase I Study of YY-20394 Given Orally to Patients With Relapsed or Refractory B Cell Hematologic Malignancies

Protocol YY-20394-001 is a phase I open-label, first in human, dose escalation study to assess the tolerability, pharmacokinetics (PK) and efficacy of YY-20394 in patients with relapse or refractory B cell malignant hematological tumor.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a two-part study comprised of a dose escalation part and a dose expansion part.

In the dose escalation part single patient cohorts will be dosed until a single related toxicity of Grade ≥ 3 or a Dose Limiting Toxicity (DLT) is observed. If this occurs, the study will switch to a conventional oncology 3+3 design (3 patients per dose cohort, with the potential to add an additional 3 patients if toxicity is observed) and escalation will continue until the maximum tolerated dose (MTD) is reached and a recommended Phase II (RP2D) dose is determined. Once the MTD is established a separate dose expansion part will enroll up total additional 12 patients at the RP2D.

In this clinical trial, YY-20394 is given orally once daily. A treatment cycle is defined as 28 days. YY-20394 was given until disease progression, unacceptable toxicity, or withdrawal from the study. The protocol was initiated with a single-patient cohort, treated with oral YY-20394 20 mg once daily (QD). Subsequent cohorts used a 3+3 design and evaluated doses of 40-320mg QD. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Efficacy was assessed according to IWG-NHL and CLL consensus response criteria.

Study Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Peking Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yuqin Song, MD,PhD
        • Sub-Investigator:
          • Meifeng Tu, MD,PhD
        • Sub-Investigator:
          • Lingyan Ping, MD,PhD
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Not yet recruiting
        • Jiangsu Province Hospital
        • Sub-Investigator:
          • Meifeng Tu, MD,PhD
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jianyong Li, MD,PhD
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Hematology Hospital of Chinese Academy of Medical Sciences
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lugui Qiu, MD,PhD
        • Sub-Investigator:
          • Junyuan Qi, MD,PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Males and/or females over age 18
  2. Histologically or cytologically confirmed B cell malignancies
  3. Eastern Cooperative Oncology Group performance status of 0 to 2
  4. Life expectancy of at least 3 months
  5. At least one measurable lesion by Computed Tomography(CT) or Magnetic Resonance Imaging(MRI) according to, which is not in irradiated area (only for expansion phase)

  6. Acceptable hematologic status:

    Absolute neutrophil count(ANC)≥1.0×109/L; Platelet count(PLT)≥70×109/L; Hemoglobin(Hb)≥80 g/L; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN); Alanine aminotransferase(ALT)≤1.5×ULN; Aspartate aminotransferase(AST)≤1.5×ULN; Blood urea nitrogen(BUN)≤1×ULN; Creatinine(Cr)≤1×ULN; Left Ventricular Ejection Fractions(LVEF)≥50%； QTcF：male<450 ms,female<470 ms

  7. The washout period from the last time accepting any anti-tumor treatment (including radiation therapy, chemotherapy, hormone therapy, surgery, or molecular targeted therapy) to participating in this test should be 4 weeks or more.
  8. The last time participate in an investigational drug or device study should be more than one month prior to study entry.
  9. Ability to understand the purposes and risks of the study
  10. Availability of the signed informed consent forms (ICFs) approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC) of the study site obtained before entering the study.

Exclusion Criteria:

  1. Previously treated with PI3Kδ inhibitors and cause disease progression.
  2. Any anti-tumor treatment, within 4 weeks prior to study entry.
  3. There are third interstitial effusions (such as massive pleural effusion and ascites) which can not be controlled by drainage or other methods.
  4. The dosage of steroid hormone (prednisone equivalent) was greater than 20mg/ days, and lasted for more than 14 days.
  5. Medical history of difficulty in swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
  6. During the study period, drugs that may prolong the QT (such as anti arrhythmic drugs) could not be interrupted.
  7. Patients with central nervous system (CNS) involvement.
  8. Allergy, or known to be allergic to the drug.
  9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy(such as pneumonia).
  10. Known infection with human immunodeficiency virus (HIV), hepatitis B virus(HBV), or hepatitis C virus (HCV).
  11. History of immunodeficiency, including HIV positive test, other acquired or congenital immunodeficiency disorders, organ transplantation or allogeneic bone marrow transplantation.
  12. Autologous hematopoietic stem cell transplantation was received within 90 days before the first dose treatment.
  13. Has suffered from any heart disease, including: (1) angina pectoris; (2) medicated or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) any other heart disease judged by the researchers not suitable for the test.
  14. The baseline pregnancy test was positive in pregnant women, lactating women or fertile women.
  15. According to the judgement of the researcher, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the study (such as severe hypertension, diabetes, thyroid diseases, etc.).
  16. Receiving granulocyte colony-stimulating factor(GCSF) or blood transfusion within 7 days before screening.
  17. Patients suffering from other primary malignant tumors in the past 5 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: YY-20394

YY-20394 is a selective inhibitor of the delta isoform of phosphatidylinositol 3- kinase (PI3Kδ).

YY-20394 for clinical use is presented as a sterile tablets at 20 mg, or 100 mg doses. The drug product is intended for oral administration.Preset cohorts of 3-6 subjects will be enrolled sequentially at doses of 20, 40, 80, 140, 200, 260 and 320 mg/day.
Drug: YY-20394
YY-20394 is a new type of PI3K-δ selective inhibitor which differs structurally from idelalisib and its analogs, showing high potency against PI3Kδ, but with markedly improved selectivity (>1,000-fold selectivity for PI3K-δ versus PI3Kγ). This higher selectivity for PI3Kδ may decrease the risk of serious infection seen with idelalisib and especially with duvelisib due to strong immune suppression.Preclinical evaluation has demonstrated improved efficacy and safety for YY-20394 compared to idelalisib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limited toxicities evaluated with NCI-CTC AE v4.0
Time Frame: within 28 days after the first dose
Incidence of dose limited toxicities and associated dose of YY-20394
within 28 days after the first dose
Adverse events evaluated by NCI CTCAE v4.0
Time Frame: from the first dose to within 30 days after the last dose
Incidence of adverse events and associated dose of YY-20394
from the first dose to within 30 days after the last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: within 30 days after the last dose
the proportion of subjects who have a Complete Response or Partial Response
within 30 days after the last dose
Disease control rate
Time Frame: within 30 days after the last dose
the proportion of subjects who have a Complete Response or Partial Response
within 30 days after the last dose
Plasma concentration of YY-20394
Time Frame: within 56 days after the first dose
This composite endpoint will measure the plasma concentration of YY-20394.
within 56 days after the first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai YingLi Pharmaceutical Co. Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 25, 2017

Primary Completion (Anticipated)

March 30, 2019

Study Completion (Anticipated)

May 30, 2019

Study Registration Dates

First Submitted

November 16, 2018

First Submitted That Met QC Criteria

November 26, 2018

First Posted (Actual)

November 28, 2018

Study Record Updates

Last Update Posted (Actual)

December 10, 2018

Last Update Submitted That Met QC Criteria

December 6, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YY-20394-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on B-cell Chronic Lymphocytic Leukemia

Clinical Trials on YY-20394

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malaysia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe