Clinical Trials List
Protocol Number54767414NKT2001
2017-01-15 - 2020-02-28
Phase II
Terminated2
Study ended1
An Open Label, Phase 2 Study to Assess the Clinical Efficacy and Safety of Daratumumab in Patients With Relapsed or Refractory Natural Killer/T-Cell Lymphoma, Nasal Type
-
Trial Applicant
Johnson & Johnson
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wen-Chien Chou Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- YA-FANG CHEN Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- 劉高郎 Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- 陳尹愷 Division of Hematology & Oncology
- 施怡倫 Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- Chien-Chin Lin Division of Hematology & Oncology
- RUOH-FANG YEN Division of Hematology & Oncology
- - - Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Ching Yun Hsieh Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Study ended
Condition/Disease
Relapsed or Refractory Natural Killer/T-Cell Lymphoma, Nasal Type
Objectives
Objective response rate (ORR) is defined as the proportion of subjects who achieve CR or PR per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin lymphoma: LUGANO classification based on BICR.
Test Drug
Daratumumab
Active Ingredient
Dosage Form
Dosage
100mg/5ml
Endpoints
Primary Objective
The primary objective of the study is to evaluate the efficacy of daratumumab in subjects with
NKTCL by ORR including complete response (CR) and partial response (PR) based on a blinded
independent central review (BICR) per Revised Criteria for Response Assessment of Hodgkin and
non-Hodgkin Lymphoma: LUGANO classifcation.
12
Secondary Objectives
The secondary objectives are:
• To evaluate the efficacy of daratumumab in NKTCL by CR rate, progression free survival
(PFS), duration of response (DoR), time to response based on a BICR, and OS
• To evaluate safety and tolerability
• To evaluate PK and immunogenicity.
The primary objective of the study is to evaluate the efficacy of daratumumab in subjects with
NKTCL by ORR including complete response (CR) and partial response (PR) based on a blinded
independent central review (BICR) per Revised Criteria for Response Assessment of Hodgkin and
non-Hodgkin Lymphoma: LUGANO classifcation.
12
Secondary Objectives
The secondary objectives are:
• To evaluate the efficacy of daratumumab in NKTCL by CR rate, progression free survival
(PFS), duration of response (DoR), time to response based on a BICR, and OS
• To evaluate safety and tolerability
• To evaluate PK and immunogenicity.
Inclution Criteria
1. At least 18 years of age
2. Documented as histologically confirmed extranodal NK/T-cell lymphoma, nasal type
according to the World Health Organization (WHO) classification,
10,13,20 and the
pathology report will be verified by the Sponsor.
3. Criterion modified per Amendment 1:
3.1 Failed (relapsed or refractory after achieving complete or partial remission) at least 1
line of chemotherapy, and who, according to treating physician or investigator, is not
candidate to receive other treatment modalities.
4. Criterion modified per Amendment 1:
4.1 At least 1 measurable site of disease (see Section 8.2.1), which should be positive
18F-fluorodeoxyglucose (FDG) uptake in nodal or extranodal sites on positron emission
tomography (PET) scan.
5. ECOG performance status score of 0, 1 or 2. (refer Attachment 1) and life expectancy
≥ 3 months.
6. Subject must have pretreatment clinical laboratory values meeting the following criteria
during the Screening Phase:
a. hemoglobin ≥7.5 g/dL (≥4.65 mmol/L) without transfusion support
within 7 days;
b. absolute neutrophil count (ANC) ≥0.75x109
/L (ie, ≥750/µL) without
growth factor support within 7 days;
c. platelet count ≥50x109
/L without transfusion support within 7 days;
d. aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN);
e. alanine aminotransferase (ALT) ≤2.5 x ULN;
f. total bilirubin ≤1.5 x ULN, except in subjects with congenital
bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin
≤1.5 x ULN required);
g. calculated creatinine clearance of ≥30 mL/min (refer Attachment 5:
Calculation of Creatinine Clearance using Cockcroft-Gault formula);
7. Criterion modified per Amendment 1:
7.1 Women of childbearing potential must commit to either abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control
simultaneously. This includes one highly effective form of contraception (tubal ligation,
intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal
rings or implants] or partner's vasectomy) and one additional effective contraceptive
method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception
must begin 4 weeks prior to dosing. Reliable contraception is indicated even where
there has been a history of infertility, unless due to hysterectomy.
8. Criterion modified per Amendment 1:
8.1 A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all menmust also not donate sperm during the study and for 3 months after receiving the final dose of study drug.
9. Criterion removed per Amendment 1
10. Criterion removed per Amendment 1
11. Criterion removed per Amendment 1
12. A woman of childbearing potential must have a negative serum/urine pregnancy test
(highly sensitive serum [-human chorionic gonadotropin]) within 14 days prior to the
first study agent administration.
13. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF
14. Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.
2. Documented as histologically confirmed extranodal NK/T-cell lymphoma, nasal type
according to the World Health Organization (WHO) classification,
10,13,20 and the
pathology report will be verified by the Sponsor.
3. Criterion modified per Amendment 1:
3.1 Failed (relapsed or refractory after achieving complete or partial remission) at least 1
line of chemotherapy, and who, according to treating physician or investigator, is not
candidate to receive other treatment modalities.
4. Criterion modified per Amendment 1:
4.1 At least 1 measurable site of disease (see Section 8.2.1), which should be positive
18F-fluorodeoxyglucose (FDG) uptake in nodal or extranodal sites on positron emission
tomography (PET) scan.
5. ECOG performance status score of 0, 1 or 2. (refer Attachment 1) and life expectancy
≥ 3 months.
6. Subject must have pretreatment clinical laboratory values meeting the following criteria
during the Screening Phase:
a. hemoglobin ≥7.5 g/dL (≥4.65 mmol/L) without transfusion support
within 7 days;
b. absolute neutrophil count (ANC) ≥0.75x109
/L (ie, ≥750/µL) without
growth factor support within 7 days;
c. platelet count ≥50x109
/L without transfusion support within 7 days;
d. aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN);
e. alanine aminotransferase (ALT) ≤2.5 x ULN;
f. total bilirubin ≤1.5 x ULN, except in subjects with congenital
bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin
≤1.5 x ULN required);
g. calculated creatinine clearance of ≥30 mL/min (refer Attachment 5:
Calculation of Creatinine Clearance using Cockcroft-Gault formula);
7. Criterion modified per Amendment 1:
7.1 Women of childbearing potential must commit to either abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control
simultaneously. This includes one highly effective form of contraception (tubal ligation,
intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal
rings or implants] or partner's vasectomy) and one additional effective contraceptive
method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception
must begin 4 weeks prior to dosing. Reliable contraception is indicated even where
there has been a history of infertility, unless due to hysterectomy.
8. Criterion modified per Amendment 1:
8.1 A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all menmust also not donate sperm during the study and for 3 months after receiving the final dose of study drug.
9. Criterion removed per Amendment 1
10. Criterion removed per Amendment 1
11. Criterion removed per Amendment 1
12. A woman of childbearing potential must have a negative serum/urine pregnancy test
(highly sensitive serum [-human chorionic gonadotropin]) within 14 days prior to the
first study agent administration.
13. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF
14. Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.
Exclusion Criteria
1. Criterion modified per Amendment 1:
1.1 No fresh or archived FFPE tumor samples for retrospective biomarker determination
2. Received daratumumab or other anti-CD38 therapies previously
3. Chemotherapy or radiotherapy within 3 weeks before the first study agent
administration, or corticosteroids as part of disease treatment within 2 weeks before the
first study agent administration, with the exception of an emergency use of
corticosteroids such as in the management of severe lymphoma symptoms or lifethreatening allergic reaction.
4. Previous allogenic stem cell transplant; or autologous stem cell transplant within
12 weeks before the first administration of the study drug
5. History of active malignancy (other than NKTCL) within 2 years before the first study
drug administration (exceptions are adequately treated squamous and basal cell
carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive
lesion that in the opinion of the investigator, with concurrence with the sponsor's study
responsible physician, is considered cured with minimal risk of recurrence within 2
years)
6. Clinical symptoms of central nervous system (CNS) involvement
7. Subject has either of the following:a. Known chronic obstructive pulmonary disease (COPD) with a Forced
Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that
FEV1 testing is required for patients suspected of having COPD and subjects
must be excluded if FEV1 <50% of predicted
b. Known moderate or severe persistent asthma within the past 2 years (refer
Attachment 4: National Heart, Lung, and Blood Institute (NHLBI) table of
asthma severity), or uncontrolled asthma of any classification. (Note: subjects
who currently have controlled intermittent asthma or controlled mild persistent
asthma are allowed to participate in the study)
8
8.1
Criterion modified per Amendment 4:
Seropositive for hepatitis B or hepatitis C.
Note: Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg
negative but positive for antibodies to hepatitis B core antigen [Anti-HBc] and/or
antibodies to hepatitis B surface antigen [Anti-HBs]) must be screened using real-time
polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.
Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic
findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic
marker) AND a known history of prior HBV vaccination, do not need to be tested for
HBV DNA by PCR.
If Hepatitis C antibody is positive, RNA PCR needs to be performed and confirmed
negative prior to the first study agent administration.
9. Seropositive for human immunodeficiency virus (HIV)
10. Unresolved or unstable, serious toxicity from prior administration of another
investigational drug and/or of prior cancer treatment.
11. Subject has any concurrent medical condition or psychiatric condition or disease (eg,
active infection, diabetes mellitus, acute diffuse infiltrative pulmonary disease) that is
likely to interfere with study procedures or results, or that in the opinion of the
investigator would constitute a hazard for participating in this study.
12. Criterion modified per Amendment 1:
12.1 Subject has clinically significant cardiac disease, including:
a. Myocardial infarction within 6 months before the first study agent
administration, or unstable or uncontrolled disease/condition related to or
affecting cardiac function (eg, unstable angina, congestive heart failure, New
York Heart Association Class III-IV)
b. Uncontrolled cardiac arrhythmia (Common Terminology Criteria for Adverse
Events [CTCAE] [most recent version] Grade 3 or higher) or clinically
significant ECG abnormalities
c. Screening 12-lead ECG showing a baseline QT interval as corrected (QTc)
>470 msec.
13. Known allergies, hypersensitivity, corticosteroids, monoclonal antibodies or human
proteins, or their excipients (refer to respective package inserts or IB), or known
sensitivity to mammalian-derived products18
14. Known or suspected of not being able to comply with the study protocol (eg, because
of alcoholism, drug dependency, or psychological disorder) or the subject has any
condition for which, in the opinion of the investigator, participation would not be in the
best interest of the subject (eg, compromise their well-being) or that could prevent,
limit, or confound the protocol-specified assessments
15. Invasive investigational medical device within 4 weeks before the screening period or
is currently enrolled in an interventional investigational study
16. Vaccination with live attenuated vaccines within 4 weeks of first study agent
administration.
17. Pregnant or lactating
1.1 No fresh or archived FFPE tumor samples for retrospective biomarker determination
2. Received daratumumab or other anti-CD38 therapies previously
3. Chemotherapy or radiotherapy within 3 weeks before the first study agent
administration, or corticosteroids as part of disease treatment within 2 weeks before the
first study agent administration, with the exception of an emergency use of
corticosteroids such as in the management of severe lymphoma symptoms or lifethreatening allergic reaction.
4. Previous allogenic stem cell transplant; or autologous stem cell transplant within
12 weeks before the first administration of the study drug
5. History of active malignancy (other than NKTCL) within 2 years before the first study
drug administration (exceptions are adequately treated squamous and basal cell
carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive
lesion that in the opinion of the investigator, with concurrence with the sponsor's study
responsible physician, is considered cured with minimal risk of recurrence within 2
years)
6. Clinical symptoms of central nervous system (CNS) involvement
7. Subject has either of the following:a. Known chronic obstructive pulmonary disease (COPD) with a Forced
Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that
FEV1 testing is required for patients suspected of having COPD and subjects
must be excluded if FEV1 <50% of predicted
b. Known moderate or severe persistent asthma within the past 2 years (refer
Attachment 4: National Heart, Lung, and Blood Institute (NHLBI) table of
asthma severity), or uncontrolled asthma of any classification. (Note: subjects
who currently have controlled intermittent asthma or controlled mild persistent
asthma are allowed to participate in the study)
8
8.1
Criterion modified per Amendment 4:
Seropositive for hepatitis B or hepatitis C.
Note: Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg
negative but positive for antibodies to hepatitis B core antigen [Anti-HBc] and/or
antibodies to hepatitis B surface antigen [Anti-HBs]) must be screened using real-time
polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.
Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic
findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic
marker) AND a known history of prior HBV vaccination, do not need to be tested for
HBV DNA by PCR.
If Hepatitis C antibody is positive, RNA PCR needs to be performed and confirmed
negative prior to the first study agent administration.
9. Seropositive for human immunodeficiency virus (HIV)
10. Unresolved or unstable, serious toxicity from prior administration of another
investigational drug and/or of prior cancer treatment.
11. Subject has any concurrent medical condition or psychiatric condition or disease (eg,
active infection, diabetes mellitus, acute diffuse infiltrative pulmonary disease) that is
likely to interfere with study procedures or results, or that in the opinion of the
investigator would constitute a hazard for participating in this study.
12. Criterion modified per Amendment 1:
12.1 Subject has clinically significant cardiac disease, including:
a. Myocardial infarction within 6 months before the first study agent
administration, or unstable or uncontrolled disease/condition related to or
affecting cardiac function (eg, unstable angina, congestive heart failure, New
York Heart Association Class III-IV)
b. Uncontrolled cardiac arrhythmia (Common Terminology Criteria for Adverse
Events [CTCAE] [most recent version] Grade 3 or higher) or clinically
significant ECG abnormalities
c. Screening 12-lead ECG showing a baseline QT interval as corrected (QTc)
>470 msec.
13. Known allergies, hypersensitivity, corticosteroids, monoclonal antibodies or human
proteins, or their excipients (refer to respective package inserts or IB), or known
sensitivity to mammalian-derived products18
14. Known or suspected of not being able to comply with the study protocol (eg, because
of alcoholism, drug dependency, or psychological disorder) or the subject has any
condition for which, in the opinion of the investigator, participation would not be in the
best interest of the subject (eg, compromise their well-being) or that could prevent,
limit, or confound the protocol-specified assessments
15. Invasive investigational medical device within 4 weeks before the screening period or
is currently enrolled in an interventional investigational study
16. Vaccination with live attenuated vaccines within 4 weeks of first study agent
administration.
17. Pregnant or lactating
The Estimated Number of Participants
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Taiwan
9 participants
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Global
32 participants
