Clinical Trials List
Protocol NumberPCYC-1140-IM
NCT Number(ClinicalTrials.gov Identfier)NCT02959944
2017-02-10 - 2020-01-30
Phase III
Terminated2
ICD-9279.8
Other specified disorders involving the immune mechanism
A Randomized, Double-Blind Phase 3 Study of Ibrutinib in Combination With Corticosteroids Versus Placebo in Combination With Corticosteroids in Subjects With New Onset Chronic Graft Versus Host Disease (cGVHD)
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Trial Applicant
ICON Clinical Research Pte Ltd
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Sponsor
Pharmacyclics LLC.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- Jih-Luh Tang Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- 張修豪 Division of Pediatrics
- Tai-Chung Huang Division of Hematology & Oncology
- MENG-YAO LU Division of Pediatrics
- 李啟誠 Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- 劉家豪 Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- YUNG-LI YANG Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Chronic Graft Versus Host Disease (cGVHD)
Objectives
Primary Objective:To evaluate the efficacy of ibrutinib in combination with prednisone(Arm A) versus placebo in combination with prednisone (Arm B) basedon the response rate at 24 weeks as determined by NIH ConsensusDevelopment Project criteria in subjects with new onset moderate tosevere cGVHD.Secondary Objectives:To compare the two treatment arms in terms of the following:Efficacy Proportion of subjects obtaining steroid dose level less than0.15 mg/kg/d at 24 weeks Withdrawal of all immunosuppressants (with the exception ofibrutinib/placebo) at 48 weeks Overall survival (OS) Response rate at 48 weeksSafety Safety and tolerability Differences in steroid-related morbidities (eg, hyperglycemia,hypertension)
Test Drug
Imbruvica®
Active Ingredient
Ibrutinib
Dosage Form
capsule
Dosage
140mg
Endpoints
Primary Efficacy Analysis:
The primary efficacy endpoint of this study is the response rate at
24 weeks (ie, the proportion of responders [CR or PR] at 24 weeks).
Response will be defined by the NIH Consensus Development Project
Criteria (2014) and must occur:
In the absence of new systemic therapy for cGVHD
In the absence of relapse or return of the underlying disease that
was the indication for transplant, or death
Response rates will be compared between the two treatment arms using
the chi-square statistical test.
Secondary Efficacy Analysis:
Steroid dose reduction to a level of less than 0.15 mg/kg/d at
24 weeks: the proportion of subjects who have steroid dose reduced
by 24 weeks will be compared between the two treatment arms
Withdrawal of all immunosuppressants (with the exception of
ibrutinib/placebo) at 48 weeks will be compared between two
treatment arms
Overall survival (OS): Overall survival is defined from
randomization to death and will be compared between the two
treatment arms using the log rank test
Response rates at 48 weeks will be compared between the two
treatment arms
The primary efficacy endpoint of this study is the response rate at
24 weeks (ie, the proportion of responders [CR or PR] at 24 weeks).
Response will be defined by the NIH Consensus Development Project
Criteria (2014) and must occur:
In the absence of new systemic therapy for cGVHD
In the absence of relapse or return of the underlying disease that
was the indication for transplant, or death
Response rates will be compared between the two treatment arms using
the chi-square statistical test.
Secondary Efficacy Analysis:
Steroid dose reduction to a level of less than 0.15 mg/kg/d at
24 weeks: the proportion of subjects who have steroid dose reduced
by 24 weeks will be compared between the two treatment arms
Withdrawal of all immunosuppressants (with the exception of
ibrutinib/placebo) at 48 weeks will be compared between two
treatment arms
Overall survival (OS): Overall survival is defined from
randomization to death and will be compared between the two
treatment arms using the log rank test
Response rates at 48 weeks will be compared between the two
treatment arms
Inclution Criteria
Eligible subjects will meet all of the following key criteria:
1. New onset moderate or severe cGVHD as defined by the NIH
Consensus Development Project Criteria (2014).
2. History of an allogeneic hematopoietic cell transplant.
3. Need for systemic treatment with corticosteroids for cGVHD.
4. No previous systemic treatment for cGVHD (including
extracorporeal photopheresis [ECP]).
5. Participants may be receiving other immunosuppressants for the
prophylaxis or treatment of acute GVHD but the doses of these
medications must have been stable for at least 2 weeks prior to
Screening. Prednisone dose must also be at or below 0.5 mg/kg/d at
the time of randomization unless started within the previous 7 days
for cGVHD.
6. Participants may have received pre-transplant ibrutinib for other
reasons besides cGVHD such as for the treatment of leukemia or
lymphoma, but must not have received a BTK inhibitor since the
time of transplant.
7. Age ≥12 years old.
8. Karnofsky or Lansky (subjects <16 years) performance score ≥60.
9. Adequate hepatic and renal function defined as:
AST, ALT ≤3 x ULN (unless of non-hepatic origin). If AST/ALT increase is associated with cGVHD then 5 x ULN
is acceptable
Total bilirubin ≤1.5 x ULN (unless of non-hepatic origin or due
to Gilbert’s Syndrome)
Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault
formula)
10. Adequate hematological function defined as:
Absolute neutrophil count ≥1.0 x 109
/L and off growth factor
support for 7 days
Platelets ≥30 x 109
/L and no transfusion for 7 days
11. PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN (unless
abnormalities are unrelated to coagulopathy or bleeding disorder).
When treated with warfarin or other vitamin K antagonist, then
INR ≤3.0.
Ethical/Other
12. Male and female subjects of reproductive potential who agree to
use both a highly effective methods of birth control (eg, implants,
injectables, combined oral contraceptives, some intrauterine
devices [IUDs], complete abstinence1
, or sterilized partner) and a
barrier method (eg, condoms, cervical ring, sponge, etc) during the
period of therapy and for 90 days for both females and males after
the last dose of study drug.
1. New onset moderate or severe cGVHD as defined by the NIH
Consensus Development Project Criteria (2014).
2. History of an allogeneic hematopoietic cell transplant.
3. Need for systemic treatment with corticosteroids for cGVHD.
4. No previous systemic treatment for cGVHD (including
extracorporeal photopheresis [ECP]).
5. Participants may be receiving other immunosuppressants for the
prophylaxis or treatment of acute GVHD but the doses of these
medications must have been stable for at least 2 weeks prior to
Screening. Prednisone dose must also be at or below 0.5 mg/kg/d at
the time of randomization unless started within the previous 7 days
for cGVHD.
6. Participants may have received pre-transplant ibrutinib for other
reasons besides cGVHD such as for the treatment of leukemia or
lymphoma, but must not have received a BTK inhibitor since the
time of transplant.
7. Age ≥12 years old.
8. Karnofsky or Lansky (subjects <16 years) performance score ≥60.
9. Adequate hepatic and renal function defined as:
AST, ALT ≤3 x ULN (unless of non-hepatic origin). If AST/ALT increase is associated with cGVHD then 5 x ULN
is acceptable
Total bilirubin ≤1.5 x ULN (unless of non-hepatic origin or due
to Gilbert’s Syndrome)
Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault
formula)
10. Adequate hematological function defined as:
Absolute neutrophil count ≥1.0 x 109
/L and off growth factor
support for 7 days
Platelets ≥30 x 109
/L and no transfusion for 7 days
11. PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN (unless
abnormalities are unrelated to coagulopathy or bleeding disorder).
When treated with warfarin or other vitamin K antagonist, then
INR ≤3.0.
Ethical/Other
12. Male and female subjects of reproductive potential who agree to
use both a highly effective methods of birth control (eg, implants,
injectables, combined oral contraceptives, some intrauterine
devices [IUDs], complete abstinence1
, or sterilized partner) and a
barrier method (eg, condoms, cervical ring, sponge, etc) during the
period of therapy and for 90 days for both females and males after
the last dose of study drug.
Exclusion Criteria
Subjects are excluded if any of the following key criteria are met:
1. Received any previous systemic treatment for cGVHD (with the
exception of systemic corticosteroids started for cGVHD within
7 days of randomization).
2. Inability to begin a prednisone dose ≥0.5 mg/kg/d for the treatment
of cGVHD.
3. Received any investigational agent ≤28 days before randomization.
4. Currently active, clinically significant cardiovascular disease, such
as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure
as defined by the New York Heart Association Functional
Classification; or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to
randomization.
5. Any uncontrolled active systemic infection or active infection
requiring systemic treatment that was ongoing ≤7 days before
randomization.
6. Progressive underlying malignant disease or any post-transplant
lymphoproliferative disease.
7. History of other malignancy (not including the underlying
malignancy that was the indication for transplant), with the
following exceptions:
Malignancy treated with curative intent and with no evidence
of active disease present for more than 3 years prior to
Screening and felt to be at low risk for recurrence by treating
physician
Adequately treated nonmelanomatous skin cancer or lentigo
maligna melanoma without current evidence of disease
Adequately treated cervical carcinoma in situ without current
evidence of disease
8. Subject has a concurrent illness which in the opinion of the
investigator may interfere with the treatment and evaluation of the
subject.
9. Known bleeding disorders (eg, von Willebrand’s disease or
hemophilia).
10. History of stroke or intracranial hemorrhage within 6 months prior
to randomization.
11. Known history of human immunodeficiency virus (HIV).
12. Subject with chronic liver disease with hepatic impairment per
Child-Pugh classification Class B or C (Appendix E).
13. Active hepatitis C virus (HCV) or hepatitis B virus (HBV).
Subjects who are positive for hepatitis B core antibody or hepatitis
B surface antigen or hepatitis C antibody must have a negative
polymerase chain reaction (PCR) result before randomization.
Those who are PCR positive will be excluded.
14. Vaccinated with live, attenuated vaccines within 4 weeks of first
dose of study drug.
15. Major surgery within 4 weeks of first dose of study drug.
16. Any life-threatening illness, medical condition, or organ system
dysfunction that, in the investigator’s opinion, could compromise
the subject’s safety or put the study outcomes at undue risk.
17. Unable to swallow capsules or malabsorption syndrome, disease
significantly affecting gastrointestinal function, or resection of the
stomach or small bowel, symptomatic inflammatory bowel disease
or ulcerative colitis, or partial or complete bowel obstruction.
18. Requires treatment with a strong cytochrome P450 (CYP) 3A
inhibitor (see Appendix D) with the exception of strong CYP3A
inhibitors used for anti-fungal prophylaxis (eg, posaconazole).
19. Female subject who is pregnant, breastfeeding, or planning to
become pregnant while enrolled in this study or within 3 months of
last dose study drug. Male subject who plans to father a child while
enrolled in this study or within 3 months after the last dose of study
drug.
20. Unwilling or unable to participate in all required study evaluations
and procedures.
21. Unable to understand the purpose and risks of the study and to
provide a signed and dated informed consent form (ICF) and
authorization to use protected health information (in accordance
with national and local subject privacy regulations).
1. Received any previous systemic treatment for cGVHD (with the
exception of systemic corticosteroids started for cGVHD within
7 days of randomization).
2. Inability to begin a prednisone dose ≥0.5 mg/kg/d for the treatment
of cGVHD.
3. Received any investigational agent ≤28 days before randomization.
4. Currently active, clinically significant cardiovascular disease, such
as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure
as defined by the New York Heart Association Functional
Classification; or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to
randomization.
5. Any uncontrolled active systemic infection or active infection
requiring systemic treatment that was ongoing ≤7 days before
randomization.
6. Progressive underlying malignant disease or any post-transplant
lymphoproliferative disease.
7. History of other malignancy (not including the underlying
malignancy that was the indication for transplant), with the
following exceptions:
Malignancy treated with curative intent and with no evidence
of active disease present for more than 3 years prior to
Screening and felt to be at low risk for recurrence by treating
physician
Adequately treated nonmelanomatous skin cancer or lentigo
maligna melanoma without current evidence of disease
Adequately treated cervical carcinoma in situ without current
evidence of disease
8. Subject has a concurrent illness which in the opinion of the
investigator may interfere with the treatment and evaluation of the
subject.
9. Known bleeding disorders (eg, von Willebrand’s disease or
hemophilia).
10. History of stroke or intracranial hemorrhage within 6 months prior
to randomization.
11. Known history of human immunodeficiency virus (HIV).
12. Subject with chronic liver disease with hepatic impairment per
Child-Pugh classification Class B or C (Appendix E).
13. Active hepatitis C virus (HCV) or hepatitis B virus (HBV).
Subjects who are positive for hepatitis B core antibody or hepatitis
B surface antigen or hepatitis C antibody must have a negative
polymerase chain reaction (PCR) result before randomization.
Those who are PCR positive will be excluded.
14. Vaccinated with live, attenuated vaccines within 4 weeks of first
dose of study drug.
15. Major surgery within 4 weeks of first dose of study drug.
16. Any life-threatening illness, medical condition, or organ system
dysfunction that, in the investigator’s opinion, could compromise
the subject’s safety or put the study outcomes at undue risk.
17. Unable to swallow capsules or malabsorption syndrome, disease
significantly affecting gastrointestinal function, or resection of the
stomach or small bowel, symptomatic inflammatory bowel disease
or ulcerative colitis, or partial or complete bowel obstruction.
18. Requires treatment with a strong cytochrome P450 (CYP) 3A
inhibitor (see Appendix D) with the exception of strong CYP3A
inhibitors used for anti-fungal prophylaxis (eg, posaconazole).
19. Female subject who is pregnant, breastfeeding, or planning to
become pregnant while enrolled in this study or within 3 months of
last dose study drug. Male subject who plans to father a child while
enrolled in this study or within 3 months after the last dose of study
drug.
20. Unwilling or unable to participate in all required study evaluations
and procedures.
21. Unable to understand the purpose and risks of the study and to
provide a signed and dated informed consent form (ICF) and
authorization to use protected health information (in accordance
with national and local subject privacy regulations).
The Estimated Number of Participants
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Taiwan
9 participants
-
Global
193 participants
