Clinical trial NCT04105010: Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8)
Official title: A Phase I/II, Open-Label, Multicentre Study to Investigate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD4205 in Patients With Peripheral T Cell Lymphoma (PTCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Peripheral T Cell Lymphoma
Lead sponsor: Dizal Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-09-26
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Obtained written informed consent
2. 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.
3. Patients must have measurable disease according to the Lugano criteria.
4. 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.
5. Adequate bone marrow reserve and organ system functions.

Exclusion Criteria:

1. Any unsolved toxicity \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy (except alopecia).
2. Active infections, active or latent tuberculosis.
3. Patients with severely decreased lung function.
4. History of heart failure or QT interval prolongation.
5. Central nervous system (CNS) or leptomeningeal lymphoma.
6. History of treatment with Janus kinase (JAK) or signal transducer and activator of transcription 3 (STAT3) inhibitor.
7. Patient has undergone an allogeneic stem cell transplant. Patient had autologous stem cell transplant within 6 months.

Primary outcomes:
measure: Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Part A and Part B: Number of Participants With Adverse Events
timeFrame: The first dose until 28 days after last dose, up to approximately 3 years
measure: Part B: Duration of Response (DoR) Assessed by IRC
timeFrame: Up to approximately 3 years
measure: Part B: Complete Response Rate (CRR) Assessed by IRC
timeFrame: Up to approximately 3 years
measure: Part B: Progression Free Survival (PFS) Assessed by IRC
timeFrame: Up to approximately 3 years
measure: Part B: Time to Response (TTR) Assessed by IRC
timeFrame: Up to approximately 3 years
measure: Part A and Part B: ORR Assessed by Investigator
timeFrame: Up to approximately 3 years
measure: Part A and Part B: DoR Assessed by Investigator
timeFrame: Up to approximately 3 years
measure: Part A and Part B: CRR Assessed by Investigator
timeFrame: Up to approximately 3 years
measure: Part A and Part B: PFS Assessed by Investigator
timeFrame: Up to approximately 3 years
measure: Part B: TTR Assessed by Investigator
timeFrame: Up to approximately 3 years
measure: Part A and Part B: Maximum Plasma Concentration (Cmax) of AZD4205
timeFrame: 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).
measure: Part A and Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of AZD4205
timeFrame: 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).
measure: Part A and Part B: Cmax,ss, at Steady State of AZD4205
timeFrame: 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).
measure: Part A and Part B: AUCss, at Steady State of AZD4205
timeFrame: 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).
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: East Melbourne
country: Australia
facility: Epworth Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Kogarah
country: Australia
facility: St George Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: Sichuan University - West China Hospital
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: NanFang Hospital of Southern Medical University
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Haikou
country: China
facility: Hainan General Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Nanchang
country: China
facility: Jiangxi Province Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Samsung Medical Center
name: Won Seog Kim, PhD
role: PRINCIPAL_INVESTIGATOR
References: