Clinical Trials List
Protocol NumberME-401-003
NCT Number(ClinicalTrials.gov Identfier)NCT03768505
2019-09-01 - 2022-12-31
Phase II
Recruiting4
Terminated1
ICD-10C82.90
Follicular lymphoma, unspecified, unspecified site
A Multicenter, Open Label Single-Arm, Phase 2 Study of Zandelisib (ME-401) in Subjects With Follicular Lymphoma and Marginal Zone Lymphoma After Failure of Two or More Prior Systemic Therapies (The TIDAL Study)
-
Trial Applicant
Syneos Health
-
Sponsor
MEI Pharma Inc
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳昭勳 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- 林建良 Division of Hematology & Oncology
- 蕭聖諺 Division of Hematology & Oncology
- Shang-Wen Chen Division of Hematology & Oncology
- 高婉真 Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Li-Yuan Bai Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Su-Peng Yeh Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Yu-Min Liao Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ya-Ping Chen Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Chun-Hui Lee Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shang-Ju Wu Division of General Internal Medicine
- 田豐銘 Division of General Internal Medicine
- 柯紀綸 Division of Nuclear Medicine
- Jih-Luh Tang Division of General Internal Medicine
- Chien-Chin Lin Division of General Internal Medicine
- Tai-Chung Huang Division of General Internal Medicine
- - - Division of General Internal Medicine
- MING YAO Division of General Internal Medicine
- Huai-Hsuan Huang Division of General Internal Medicine
- 劉高郎 Division of Radiology
- 林建廷 Division of General Internal Medicine
- Chieh-Lung Cheng Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
- SHAN-CHI YU Division of Others -
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Follicular Lymphoma and Marginal Zone Lymphoma After Failure of Two or More Prior Systemic Therapies
Objectives
Primary Objectives
• To evaluate the objective response rate (ORR) of ME-401 in relapsed FL, defined as the
best response rating of complete response (CR) or partial response (PR) according to the
Lugano Response Criteria (Cheson 2014), as determined by an Independent Response
Review Committee (IRRC)
• To evaluate the tolerability of ME-401, defined as the rate of AEs requiring modified
dosing schedule or study drug discontinuation (AERDM)
Secondary Objectives
• To evaluate the efficacy of ME-401 as assessed by an IRRC:
o Duration of response (DOR) among subjects with an objective response
o Complete response (CR) rate
o Progression-free survival (PFS)
• To evaluate the efficacy of ME-401 as assessed by the Investigator:
o Objective response rate (ORR)
o Duration of response (DOR) among subjects with an objective response
o Complete response (CR) rate
o Progression-free survival (PFS)
• To evaluate overall survival (OS)
• To evaluate the safety profile of ME-401
o Overall incidence of AEs
o Time to occurrence of AERDM
• To evaluate the PK of ME-401
Test Drug
ME-401
Active Ingredient
ME-401
Dosage Form
capsule
Dosage
60
Endpoints
Primary Outcome Measures :
Objective response rate (ORR) of ME-401 in relapsed or refractory FL or MZL based on the Independent Review Committee assessment [ Time Frame: 2 years ]
ORR is measured as the proportion of subjects achieving the best response rating of CR or PR prior to first PD
Objective response rate (ORR) of ME-401 in relapsed or refractory FL or MZL based on the Independent Review Committee assessment [ Time Frame: 2 years ]
ORR is measured as the proportion of subjects achieving the best response rating of CR or PR prior to first PD
Inclution Criteria
Inclusion Criteria
1. Signed, informed consent
2. Age ≥ 18 years (or age of majority)
3. Histologically confirmed diagnosis of FL as defined in the WHO classification scheme,
limited to Grade 1, 2, or 3a (Swerdlow 2016)
4. Progression of disease after at least 2 prior systemic therapies for FL. Subjects must have
received an anti-CD20 antibody (minimum of 4 doses) and chemotherapy (minimum of
2 doses, which must have included an alkylating agent or a purine analogue), whether
administered together or as successive treatments; radioimmunotherapy, high dose therapy
and autologous stem cell transplantation, and CAR T-cell therapy are considered as one line
of therapy
Subjects will be classified as having relapsed or refractory disease to each prior systemic
therapy administered, as follows:
a. Relapsed disease: a subject who previously achieved a CR or PR to therapy but
demonstrated disease progression after a response duration of ≥ 6 months to prior
chemotherapy, immunotherapy, or radioimmunotherapy, or ≥ 12 months to prior high
dose therapy and stem cell transplantation or CAR T-cell therapy
b. Refractory disease: a subject who did not respond to therapy or demonstrated disease
progression within < 6 months of completing chemotherapy, immunotherapy or
radioimmunotherapy, or within < 12 months of completing high dose therapy and stem
cell transplantation or CAR T-cell therapy
5. No prior therapy with PI3Kδ inhibitors
6. No disease progression on prior therapy with Bruton tyrosine kinase (BTK) inhibitors
7. At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by
computed tomography (CT) scan as defined by the Lugano Classification (Cheson 2014)
a. Previously irradiated lesions should not be counted as target lesions
b. Lesions that are intended to be used to collect tissue samples for biopsy should not be
counted as target lesions
c. Bone lesions should not be counted as target lesions
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Oken 1982)
9. Adequate hematologic parameters at screening unless abnormal values due to FL per
Investigator assessment:
a. ANC ≥ 1.0 x 109
/L (≥ 1,000/mm3
)
b. Platelet count ≥ 75 x 109
/L (≥ 75,000/mm3
)
c. Hemoglobin ≥ 9.0 g/dL (≥ 90 g/L)
10. Adequate renal and hepatic function, per local laboratory reference range at Screening as
follows:
a. AST/SGOT, ALT/SGPT ≤ 2.0 x (upper limit of normal) ULN
b. Total bilirubin ≤ 2.0 x ULN or ≤ 3 x ULN for patients with Gilbert’s syndrome
c. Serum creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR)
> 50 mL/min using the Cockcroft-Gault equation (Appendix 2)
11. QT-interval corrected according to Fridericia’s formula (QTcF) ≤ 450 milliseconds (ms);
subjects with QTc > 450 msec but < 480 msec may be enrolled provided the QTc
prolongation is due to a right bundle branch block (RBBB), left bundle branch block (LBBB)
or pacemaker and is confirmed stable by a cardiologist
12. Left ventricular ejection fraction (LVEF) ≥ than institutional lower limit of normal as
measured by echocardiogram
13. Subjects must have completed any prior systemic anti-cancer treatment, radiation therapy or
surgery ≥ 4 weeks before Study Day 1, and ≥ 3 months before Study Day 1 for high dose
therapy and stem cell transplantation and CAR T-cell therapy
14. All clinically significant treatment-related toxicity from prior therapy, except for alopecia,
resolved to ≤ Grade 1 or to a new stable baseline
15. For females of childbearing potential, a negative serum pregnancy test within 28 days of
Study Day 1 and negative urine dipstick result on Study Day 1
16. For females of child-bearing potential agreement to use a medically-effective contraceptive
method that results in a failure rate of < 1% per year during the treatment period and until
60 days after ME-401 discontinuation (Appendix 4). Abstinence is acceptable if this is the
established and preferred contraceptive method for the subject
17. Male subjects agree to use an adequate method of contraception starting with the first dose of
study product through 90 days after ME-401 discontinuation (Appendix 4).
1. Signed, informed consent
2. Age ≥ 18 years (or age of majority)
3. Histologically confirmed diagnosis of FL as defined in the WHO classification scheme,
limited to Grade 1, 2, or 3a (Swerdlow 2016)
4. Progression of disease after at least 2 prior systemic therapies for FL. Subjects must have
received an anti-CD20 antibody (minimum of 4 doses) and chemotherapy (minimum of
2 doses, which must have included an alkylating agent or a purine analogue), whether
administered together or as successive treatments; radioimmunotherapy, high dose therapy
and autologous stem cell transplantation, and CAR T-cell therapy are considered as one line
of therapy
Subjects will be classified as having relapsed or refractory disease to each prior systemic
therapy administered, as follows:
a. Relapsed disease: a subject who previously achieved a CR or PR to therapy but
demonstrated disease progression after a response duration of ≥ 6 months to prior
chemotherapy, immunotherapy, or radioimmunotherapy, or ≥ 12 months to prior high
dose therapy and stem cell transplantation or CAR T-cell therapy
b. Refractory disease: a subject who did not respond to therapy or demonstrated disease
progression within < 6 months of completing chemotherapy, immunotherapy or
radioimmunotherapy, or within < 12 months of completing high dose therapy and stem
cell transplantation or CAR T-cell therapy
5. No prior therapy with PI3Kδ inhibitors
6. No disease progression on prior therapy with Bruton tyrosine kinase (BTK) inhibitors
7. At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by
computed tomography (CT) scan as defined by the Lugano Classification (Cheson 2014)
a. Previously irradiated lesions should not be counted as target lesions
b. Lesions that are intended to be used to collect tissue samples for biopsy should not be
counted as target lesions
c. Bone lesions should not be counted as target lesions
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Oken 1982)
9. Adequate hematologic parameters at screening unless abnormal values due to FL per
Investigator assessment:
a. ANC ≥ 1.0 x 109
/L (≥ 1,000/mm3
)
b. Platelet count ≥ 75 x 109
/L (≥ 75,000/mm3
)
c. Hemoglobin ≥ 9.0 g/dL (≥ 90 g/L)
10. Adequate renal and hepatic function, per local laboratory reference range at Screening as
follows:
a. AST/SGOT, ALT/SGPT ≤ 2.0 x (upper limit of normal) ULN
b. Total bilirubin ≤ 2.0 x ULN or ≤ 3 x ULN for patients with Gilbert’s syndrome
c. Serum creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR)
> 50 mL/min using the Cockcroft-Gault equation (Appendix 2)
11. QT-interval corrected according to Fridericia’s formula (QTcF) ≤ 450 milliseconds (ms);
subjects with QTc > 450 msec but < 480 msec may be enrolled provided the QTc
prolongation is due to a right bundle branch block (RBBB), left bundle branch block (LBBB)
or pacemaker and is confirmed stable by a cardiologist
12. Left ventricular ejection fraction (LVEF) ≥ than institutional lower limit of normal as
measured by echocardiogram
13. Subjects must have completed any prior systemic anti-cancer treatment, radiation therapy or
surgery ≥ 4 weeks before Study Day 1, and ≥ 3 months before Study Day 1 for high dose
therapy and stem cell transplantation and CAR T-cell therapy
14. All clinically significant treatment-related toxicity from prior therapy, except for alopecia,
resolved to ≤ Grade 1 or to a new stable baseline
15. For females of childbearing potential, a negative serum pregnancy test within 28 days of
Study Day 1 and negative urine dipstick result on Study Day 1
16. For females of child-bearing potential agreement to use a medically-effective contraceptive
method that results in a failure rate of < 1% per year during the treatment period and until
60 days after ME-401 discontinuation (Appendix 4). Abstinence is acceptable if this is the
established and preferred contraceptive method for the subject
17. Male subjects agree to use an adequate method of contraception starting with the first dose of
study product through 90 days after ME-401 discontinuation (Appendix 4).
Exclusion Criteria
1. Known active histological transformation from FL to an aggressive lymphoma: biopsy
documentation of the absence or presence of transformation is not required and left to the
Investigator’s discretion
2. Major surgical procedure within 4 weeks of Day 1
3. Any uncontrolled clinically significant illness including, but not limited to, active infections,
hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction
4. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core
antibody plus have a positive hepatitis B PCR assay; subjects with a negative PCR assay are
permitted with appropriate anti-viral prophylaxis
5. Positive HCV Ab; subjects with positive hepatitis C antibody are eligible if they are negative
for HCV by PCR
6. Ongoing or history of drug-induced pneumonitis
7. Other diagnosis of cancer that is likely to require treatment in the next 2 years, with the
exception of the following:
a. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin
b. Curatively treated carcinoma in situ of the cervix
c. Hormonal therapy for prostate cancer or prostate cancer on watch and wait
d. Adequately treated DCIS
8. History of clinically significant cardiovascular abnormalities such as congestive heart failure
(New York Heart Association classification ≥ 2 [NYHA 1994]), myocardial infarction within
6 months of study entry
9. History of clinically significant GI conditions, particularly:
a. Known GI condition that would interfere with swallowing or the oral absorption or
tolerance of study product
b. Pre-existing malabsorption syndrome or other clinical situation that would affect oral
absorption
10. Females who plan to breastfeed during study treatment and for 90 days after ending treatment
11. Subject is currently receiving an investigational agent or device or has participated in a study
of an investigational agent or device within 4 weeks of the first dose of treatment
12. Psychiatric illness/social situations that would interfere with study compliance.
documentation of the absence or presence of transformation is not required and left to the
Investigator’s discretion
2. Major surgical procedure within 4 weeks of Day 1
3. Any uncontrolled clinically significant illness including, but not limited to, active infections,
hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction
4. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core
antibody plus have a positive hepatitis B PCR assay; subjects with a negative PCR assay are
permitted with appropriate anti-viral prophylaxis
5. Positive HCV Ab; subjects with positive hepatitis C antibody are eligible if they are negative
for HCV by PCR
6. Ongoing or history of drug-induced pneumonitis
7. Other diagnosis of cancer that is likely to require treatment in the next 2 years, with the
exception of the following:
a. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin
b. Curatively treated carcinoma in situ of the cervix
c. Hormonal therapy for prostate cancer or prostate cancer on watch and wait
d. Adequately treated DCIS
8. History of clinically significant cardiovascular abnormalities such as congestive heart failure
(New York Heart Association classification ≥ 2 [NYHA 1994]), myocardial infarction within
6 months of study entry
9. History of clinically significant GI conditions, particularly:
a. Known GI condition that would interfere with swallowing or the oral absorption or
tolerance of study product
b. Pre-existing malabsorption syndrome or other clinical situation that would affect oral
absorption
10. Females who plan to breastfeed during study treatment and for 90 days after ending treatment
11. Subject is currently receiving an investigational agent or device or has participated in a study
of an investigational agent or device within 4 weeks of the first dose of treatment
12. Psychiatric illness/social situations that would interfere with study compliance.
The Estimated Number of Participants
-
Taiwan
16 participants
-
Global
184 participants
