Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8)
- Conditions
- Relapsed or Refractory Peripheral T Cell Lymphoma
- Interventions
- Registration Number
- NCT04105010
- Lead Sponsor
- Dizal Pharmaceuticals
- Brief Summary
This is a multinational, non-randomized, open-label, Phase 1/2 clinical study to evaluate the safety, tolerability and anti-tumor efficacy of AZD4205 as monotherapy in patients with peripheral T cell lymphoma (PTCL), who have relapsed from or are refractory/intolerant to standard systemic treatment.
Phase 1 part:
Around 20\~40 patients will be subsequently enrolled into 2 different dose ascending cohorts. Additional 10\~20 patients may be enrolled to further explore a selected dose defined by dose escalation cohorts.
Phase 2 part:
After the recommended phase 2 dose (RP2D) is defined, a phase 2 single-arm open-label pivotal study will be conducted to assess anti-tumor efficacy and safety of AZD4205 at RP2D in patients with refractory or relapsed PTCL.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 171
- Obtained written informed consent
- Patients must have histologically confirmed peripheral T-cell lymphoma according to the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Tumor samples are required for central pathology review to confirm the diagnosis.
- Patients must have measurable disease according to the Lugano criteria.
- Patients should be transplant-ineligible upon their entry into this study, and must have relapsed after or been refractory/intolerant to ≥ 1 (but not > 3) prior systemic therapy(ies) for PTCL.
- Adequate bone marrow reserve and organ system functions.
- Any unsolved toxicity > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy (except alopecia).
- Active infections, active or latent tuberculosis.
- Patients with severely decreased lung function.
- History of heart failure or QT interval prolongation.
- Central nervous system (CNS) or leptomeningeal lymphoma.
- History of treatment with Janus kinase (JAK) or signal transducer and activator of transcription 3 (STAT3) inhibitor.
- Patient has undergone an allogeneic stem cell transplant. Patient had autologous stem cell transplant within 6 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description golidocitinib Group A golidocitinib Group A: Open label golidocitinib at dose A, once daily (Phase 1) golidocitinib Group B golidocitinib Group B: Open label golidocitinib at dose B, once daily (Phase 1) golidocitinib Group C golidocitinib Group C: Open label golidocitinib at a selected dose, once daily (Phase 1) golidocitinib Group D golidocitinib Group D: Open label golidocitinib at the RP2D, once daily (Phase 2)
- Primary Outcome Measures
Name Time Method Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC) Up to approximately 3 years ORR is the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) based on CT scans evaluated by IRC per Lugano criteria.
- Secondary Outcome Measures
Name Time Method Part A and Part B: Number of Participants With Adverse Events The first dose until 28 days after last dose, up to approximately 3 years To evaluate the safety and tolerability of AZD4205 in patients with PTCL in terms of adverse events (AEs), such as number of participants with AEs
Part B: Duration of Response (DoR) Assessed by IRC Up to approximately 3 years DoR is the time from the date of first documented response until the date of documented progression or death due to any cause. Documented response and progression are both identified based on CT scans evaluated by IRC per Lugano criteria.
Part B: Complete Response Rate (CRR) Assessed by IRC Up to approximately 3 years CRR is the percentage of patients with at least one visit response of CR based on CT scans evaluated by IRC per Lugano criteria.
Part B: Progression Free Survival (PFS) Assessed by IRC Up to approximately 3 years PFS is the time from the date of first dosing until the date of objective disease progression or death (by any cause) regardless of whether the participant discontinues the study treatments. Progression is identified based on CT scans evaluated by IRC per Lugano criteria.
Part B: Time to Response (TTR) Assessed by IRC Up to approximately 3 years TTR is the time from the date of first dosing to the time of the initial response of PR or CR. Response is identified based on CT scans evaluated by IRC per Lugano criteria.
Part A and Part B: ORR Assessed by Investigator Up to approximately 3 years ORR is the percentage of patients with at least one visit response of CR or PR based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part A and Part B: DoR Assessed by Investigator Up to approximately 3 years DoR is the time from the date of first documented response until the date of documented progression or death due to any cause. Documented response and progression are both identified based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part A and Part B: CRR Assessed by Investigator Up to approximately 3 years CRR is the percentage of patients with at least one visit response of CR based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part A and Part B: PFS Assessed by Investigator Up to approximately 3 years PFS is the time from the date of first dosing until the date of objective disease progression or death (by any cause) regardless of whether the participant discontinues the study treatments. Progression is identified based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part B: TTR Assessed by Investigator Up to approximately 3 years TTR is the time from the date of first dosing to the time of the initial response of PR or CR. Response is identified based on CT scans evaluated by investigator per Lugano criteria.
Part A and Part B: Maximum Plasma Concentration (Cmax) of AZD4205 Cycle 1 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D). Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose.
Part A and Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of AZD4205 Cycle 1, Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D). Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule.
Part A and Part B: Cmax,ss, at Steady State of AZD4205 Cycle 2 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D). Maximum observed plasma concentration (ng/mL) at steady state, obtained directly from the observed concentration versus time data. Calculated for the multiple doses.
Part A and Part B: AUCss, at Steady State of AZD4205 Cycle 2 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D). Area under the plasma concentration-time curve from time zero to the last quantifiable time point at steady state, calculated by the linear up/log down rule
Trial Locations
- Locations (50)
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
St George Hospital
🇦🇺Kogarah, Australia
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Xiangya Hospital Central South University
🇨🇳Changsha, China
Peking University Third Hospital
🇨🇳Beijing, China
The Second Hospital of Dalian Medical University
🇨🇳Dalian, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
NanFang Hospital of Southern Medical University
🇨🇳Guangzhou, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, China
Hainan General Hospital
🇨🇳Haikou, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Anhui Provincial Cancer Hospital
🇨🇳Hefei, China
Shandong Cancer Hospital
🇨🇳Jinan, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, China
Ruijin Hospital Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, China
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Royal Hobart Hospital
🇦🇺Hobart, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Epworth Hospital
🇦🇺East Melbourne, Australia
Beijing Cancer Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, China
Beijing Hospital
🇨🇳Beijing, China
Hunan Cancer Hospital
🇨🇳Changsha, China
Sichuan University - West China Hospital
🇨🇳Chengdu, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, China
The First Hospital of Lanzhou University
🇨🇳Lanzhou, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, China
Jiangxi Province Cancer Hospital
🇨🇳Nanchang, China
Linyi Cancer Hospital
🇨🇳Linyi, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
National Cancer Center
🇰🇷Goyang, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States