Undersøgelse af BGB-11417 hos voksne deltagere med modne B-celle maligniteter
Et fase 1-studie, der evaluerer sikkerhed, tolerabilitet, farmakokinetik og foreløbig antitumoraktivitet af Bcl-2-hæmmer BGB-11417 hos voksne patienter med modne B-celle maligniteter
The purpose of this study is to evaluate the safety and tolerability of BGB-11417 monotherapy, define the maximum tolerated dose (MTD) or maximum administered dose and the recommended Phase 2 dose (RP2D) of BGB-11417 monotherapy for the selected B-cell malignancy dose finding cohorts, and evaluate the safety and tolerability of the ramp-up dosing schedule in the evaluated disease types.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This study will have 3 cohorts for determining a monotherapy MTD and ramp-up schedule: Cohort A, participants with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R NHL); Cohort B, participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with low tumor burden; Cohort C, participants with R/R CLL/SLL with high tumor burden.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100034
- Peking University First Hospital
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Beijing, Beijing Municipality, Kina, 100044
- Peking University Peoples Hospital
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Guangdong
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Guangzhou, Guangdong, Kina, 510060
- Sun Yat Sen University Cancer Center
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Shenzhen, Guangdong, Kina, 518020
- Shenzhen Peoples Hospital
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Henan
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Zhengzhou, Henan, Kina, 450000
- Henan Cancer Hospital
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Hubei
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Wuhan, Hubei, Kina, 430030
- Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
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Hunan
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Changsha, Hunan, Kina, 410013
- Hunan Cancer Hospital
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Jiangsu
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Suzhou, Jiangsu, Kina, 215006
- The First Affiliated Hospital of Soochow University
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Jiangxi
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Nanchang, Jiangxi, Kina, 330006
- The First Affiliated Hospital of Nanchang University Branch Donghu
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Kina, 200032
- Affiliated Zhongshan Hospital of Fudan University
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Zhejiang
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Hangzhou, Zhejiang, Kina, 310003
- The First Affiliated Hospital, Zhejiang University School of Medicine
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Key Inclusion Criteria:
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Confirmed diagnosis of only one of the following:
Cohort A
a. Marginal Zone Lymphoma
i. R/R extranodal, splenic or nodal disease defined as disease that has relapsed after, or been refractory to, ≥ 1 line of anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for MZL is available per investigator's assessment.
ii. Active disease requiring treatment.
b. Follicular Lymphoma
i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that has relapsed after, or been refractory to, ≥ 1 line of anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for FL is available per investigator's assessment.
ii. Active disease requiring treatment.
c. Diffuse Large B-cell Lymphoma
i. R/R DLBCL defined as disease that relapsed after, or been refractory to, at least one line of anti-CD20 antibody based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for DLBCL is available per investigator's assessment.
ii. Active disease requiring treatment.
d. Transformed indolent B-cell NHL
i. Any lymphoma otherwise eligible for Cohort A that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Cohort A.
ii. Active disease requiring treatment.
Cohorts B and C
a. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria:
i. R/R disease defined as disease that has relapsed after, or been refractory to, ≥ 1 line of standard therapy for ≥ 2 consecutive cycles, and no effective standard therapy is available per investigator's assessment.
ii. Requiring treatment based on IWCLL criteria.
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Measurable disease by computed tomography/magnetic resonance imaging, defined as:
- CLL: At least 1 lymph node > 1.5 centimeters (cm) in longest diameter and measurable in 2 perpendicular dimensions. For Cohort B, participants should not meet with the definition of high tumor burden, which is required for participants enrolled in Cohort C.
- DLBCL, FL, MZL, SLL: At least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions. For MZL isolated splenomegaly is considered to indicate measurable disease for this study. For SLL, participants in Cohort B should not meet with the definition of high tumor burden, which is required for participants enrolled in Cohort C.
Key Exclusion Criteria:
- Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
- Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.
- Known central nervous system involvement by lymphoma/leukemia.
- Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome.
- Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric cell therapy unless ≥ 6 months after cell infusion.
- Prior allogeneic stem cell transplant.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Cohort A: R/R NHL
Participants with R/R NHL, including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), or transformed NHL, will receive oral BGB-11417 until the MTD (or maximum ascending dose [MAD]) and the RP2D can be determined. |
Film-coated tablets administered orally as specified in the treatment arm.
Andre navne:
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Eksperimentel: Cohort B: R/R CLL/SLL (low tumor burden)
Participants with low tumor burden R/R CLL/SLL will receive oral BGB-11417 until the MTD (or MAD) and the RP2D can be determined. |
Film-coated tablets administered orally as specified in the treatment arm.
Andre navne:
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Eksperimentel: Cohort C: R/R CLL/SLL (high tumor burden)
Participants in this cohort will not be enrolled until the RP2D for Cohort B is established. Participants will be treated with the monotherapy ramp-up schedule and the RP2D established in Cohort B. |
Film-coated tablets administered orally as specified in the treatment arm.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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MTD af BGB-11417 som anbefalet af den bayesianske logistiske regressionsmodel eller MAD
Tidsramme: Cirka 3 år
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Cirka 3 år
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Forekomst og sværhedsgrad af tumorlysis-syndrom-relevante hændelser
Tidsramme: Cirka 3 år
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Cirka 3 år
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RP2D Of BGB-11417
Tidsramme: Approximately 3 years
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The RP2D will be decided by the sponsor and based on the safety monitoring committee recommendation considering totality of data. |
Approximately 3 years
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Incidence And Severity Of Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events (AEs) Leading To Discontinuation, And Dose-Limiting Toxicities (DLTs)
Tidsramme: Approximately 3 years
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All AEs, including DLT events, will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (or the Grading Scale for Hematologic Toxicity in CLL Studies as appropriate). |
Approximately 3 years
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Farmakokinetik (PK) vurderet ved maksimal observeret plasmakoncentration (Cmax) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet efter areal under plasmakoncentrationstidskurven fra tid 0 til tidspunktet for den sidste kvantificerbare koncentration (AUC0-t) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet efter areal under plasmakoncentrationstidskurven fra tid 0 til uendelig (AUC0-inf) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet efter tid til maksimal observeret plasmakoncentration (tmax) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet ved terminal halveringstid (t1/2) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet ved tilsyneladende total clearance af lægemiddel fra plasma efter oral administration (CL/F) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet ved tilsyneladende distributionsvolumen (Vz/F) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet efter areal under plasmakoncentrationstidskurven fra tid 0 til sidste målbar koncentration ved stabil tilstand (AUClast,ss) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet ved maksimal observeret plasmakoncentration ved stabil tilstand (Cmax,ss) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet ved trugkoncentration ved stabil tilstand (ctrough,ss) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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PK som vurderet efter tid til maksimal observeret plasmakoncentration ved stabil tilstand (tmax,ss) af BGB-11417
Tidsramme: Op til 24 timer efter dosis
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Op til 24 timer efter dosis
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Overall Response Rate (ORR) Of BGB-11417 Monotherapy
Tidsramme: Approximately 3 years
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ORR will be assessed per disease-specific response assessment guidelines as determined by the investigator. |
Approximately 3 years
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Lu Zhang, M.D., BeiGene (Suzhou) Co., Ltd.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Andre undersøgelses-id-numre
- BGB-11417-102
- CTR20211017 (Registry Identifier: ChinaDrugTrials)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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