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

NCT03757000 | Unknown Phase 1 DMC

• 1 other identifier: YY-20394-001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

B-cell Lymphoma Recurrent; B-cell Chronic Lymphocytic Leukemia

Keywords

YY-20394; B-cell Lymphoma Recurrent

Outcome Measures

Primary Outcomes (2)

• Dose limited toxicities evaluated with NCI-CTC AE v4.0

  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

  Incidence of adverse events and associated dose of YY-20394

  from the first dose to within 30 days after the last dose

Secondary Outcomes (3)

• Plasma concentration of YY-20394

  within 56 days after the first dose

• Objective response rate

  within 30 days after the last dose

• Disease control rate

  within 30 days after the last dose

Study Arms (1)

YY-20394

EXPERIMENTAL

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

Interventions

YY-20394 DRUG

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.

YY-20394

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and/or females over age 18
• Histologically or cytologically confirmed B cell malignancies
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Life expectancy of at least 3 months
• 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)
• 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
• 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.
• The last time participate in an investigational drug or device study should be more than one month prior to study entry.
• Ability to understand the purposes and risks of the study
• 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.

You may not qualify if:

• Previously treated with PI3Kδ inhibitors and cause disease progression.
• Any anti-tumor treatment, within 4 weeks prior to study entry.
• There are third interstitial effusions (such as massive pleural effusion and ascites) which can not be controlled by drainage or other methods.
• The dosage of steroid hormone (prednisone equivalent) was greater than 20mg/ days, and lasted for more than 14 days.
• 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.
• During the study period, drugs that may prolong the QT (such as anti arrhythmic drugs) could not be interrupted.
• Patients with central nervous system (CNS) involvement.
• Allergy, or known to be allergic to the drug.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy(such as pneumonia).
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus(HBV), or hepatitis C virus (HCV).
• History of immunodeficiency, including HIV positive test, other acquired or congenital immunodeficiency disorders, organ transplantation or allogeneic bone marrow transplantation.
• Autologous hematopoietic stem cell transplantation was received within 90 days before the first dose treatment.
• 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.
• The baseline pregnancy test was positive in pregnant women, lactating women or fertile women.
• 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.).

Sponsors & Collaborators

• Shanghai YingLi Pharmaceutical Co. Ltd.: lead

Study Sites (3)

Peking Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

NOT YET RECRUITING

Hematology Hospital of Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Related Publications (9)

• Eisenreich A, Rauch U. PI3K inhibitors in cardiovascular disease. Cardiovasc Ther. 2011 Feb;29(1):29-36. doi: 10.1111/j.1755-5922.2010.00206.x.

  PMID: 20626398 RESULT

• Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004 Apr 23;304(5670):554. doi: 10.1126/science.1096502. Epub 2004 Mar 11. No abstract available.

  PMID: 15016963 RESULT

• Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008 Sep 18;27(41):5497-510. doi: 10.1038/onc.2008.245.

  PMID: 18794884 RESULT

• Kong D, Yamori T. Phosphatidylinositol 3-kinase inhibitors: promising drug candidates for cancer therapy. Cancer Sci. 2008 Sep;99(9):1734-40. doi: 10.1111/j.1349-7006.2008.00891.x. Epub 2008 Jul 4.

  PMID: 18616528 RESULT

• Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, Spurgeon SE, Kahl BS, Bello C, Webb HK, Johnson DM, Peterman S, Li D, Jahn TM, Lannutti BJ, Ulrich RG, Yu AS, Miller LL, Furman RR. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014 May 29;123(22):3390-7. doi: 10.1182/blood-2013-11-535047. Epub 2014 Mar 10.

  PMID: 24615777 RESULT

• Flinn IW, Kahl BS, Leonard JP, Furman RR, Brown JR, Byrd JC, Wagner-Johnston ND, Coutre SE, Benson DM, Peterman S, Cho Y, Webb HK, Johnson DM, Yu AS, Ulrich RG, Godfrey WR, Miller LL, Spurgeon SE. Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-delta, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood. 2014 May 29;123(22):3406-13. doi: 10.1182/blood-2013-11-538546. Epub 2014 Mar 10.

  PMID: 24615776 RESULT

• Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. doi: 10.1056/NEJMoa1314583. Epub 2014 Jan 22.

  PMID: 24450858 RESULT

• Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O'Brien SM. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014 Mar 13;370(11):997-1007. doi: 10.1056/NEJMoa1315226. Epub 2014 Jan 22.

  PMID: 24450857 RESULT

• Jiang B, Qi J, Song Y, Li Z, Tu M, Ping L, Liu Z, Bao H, Xu Z, Qiu L. Phase 1 clinical trial of the PI3Kdelta inhibitor YY-20394 in patients with B-cell hematological malignancies. J Hematol Oncol. 2021 Aug 23;14(1):130. doi: 10.1186/s13045-021-01140-z.

  PMID: 34425850 DERIVED

Related Links

• Related Info
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MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hanying Bao, PhD

  Shanghai YingLi Pharmaceutical Co. Ltd.

  STUDY DIRECTOR

Central Study Contacts

Hanying Bao, MD,PhD

CONTACT

86 21-51370693; hybao@yl-pharma.com

Yuanyuan Xu, M.S.

CONTACT

86 21-51320088; yyxu@yl-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: dose escalation

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 28, 2018
• Study Start: December 25, 2017
• Primary Completion: March 30, 2019
• Study Completion: May 30, 2019
• Last Updated: December 10, 2018

Record last verified: 2018-12

Locations

CN (3)