- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01155817
Phase 1 Nilotinib in Steroid Dependent/Refractory Chronic Graft Versus Host Disease
A Phase 1 Study of Nilotinib in Steroid Dependent/Refractory Chronic Graft Versus Host Disease
PRIMARY OBJECTIVES:
Determine the safety and tolerability of nilotinib in steroid dependent / refractory cGVHD.
SECONDARY OBJECTIVES:
Determine the clinical efficacy of nilotinib in steroid dependent / refractory cGVHD.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V5Z1M9
- Gordon and Leslie Diamond Health Care Centre Hematology Administration
-
-
-
-
California
-
Stanford, California, United States, 94305
- Stanford University School of Medicine
-
-
Colorado
-
Denver, Colorado, United States, 80218
- Colorado Blood Cancer Institute
-
-
New York
-
Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
-
-
Washington
-
Seattle, Washington, United States, 98109-1024
- Fred Hutchinson Cancer Research Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:5.1.1 Steroid dependent/refractory cGVHD defined as:
- Dependent disease - Persistent cGVHD manifestations requiring a glucocorticoid dose >= prednisone 0.25 mg/kg/day (0.5 mg/kg po qod) for at least 12 weeks.
- Refractory disease - Progressive cGVHD manifestations despite treatment with a glucocorticoid dose >= prednisone 0.5 mg/kg/day (1 mg/kg po qod) for at least 4 weeks.
5.1.2 Any previous treatments for cGVHD (except nilotinib). Participants may have received nilotinib for other reasons besides cGVHD such as leukemia or solid tumor.
5.1.3 Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting nilotinib.
5.1.4 At the time of trial enrollment, participants may be receiving one or two other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting nilotinib. Monoclonal T or B cell antibodies must be discontinued at least 28 days before starting nilotinib.
5.1.5 Chronic GVHD manifestations that can be followed on physical or laboratory exam. A list of potential manifestations is presented in Appendix D.
- Skin changes
- Oral mucosa changes
- Hepatic dysfunction
5.1.6 >= 18 years old
5.1.7 Life expectancy >= 6 months.
5.1.8 Karnofsky performance status >= 60 (defined as being unable to work, able to live at home, and able to care for most personal needs but requiring occasional assistance from others).
5.1.9 Laboratory parameters:
- Creatinine < 1.5 x ULN
- ANC > 1.5 x 10^9/L
- Platelets > 100 x 10^9/L
- Total bilirubin < 1.5 x ULN
- AST (SGOT) and ALT (SGPT) < 2.5 x ULN
- Serum amylase and lipase <= 1.5 x ULN
- Alkaline phosphatase <= 2.5 x ULN
- Patients must have the following laboratory values within normal limits at the local institution lab or corrected to within normal limits with supplements prior to the first dose of study medication:
Potassium Magnesium Phosphorus Calcium
5.1.10 Oxygen saturation during exertion maintained at >= 88% on room air.
5.1.11 Ability to understand and willingness to sign a written informed consent form.
5.1.12 Females with reproductive potential must have a negative pregnancy test <= 7 days before starting nilotinib. Reproductive potential will be defined as having at least 1 menstrual period in the past 12 months. Male and female subjects with reproductive potential agree to the use of barrier contraception during their treatment and for up to 3 months after the last dose.
5.1.13 Careful rationalization of concomitant medications with the intent to discontinue or change to alternative medications when any concomitant medications are identified that have the potential to prolong the QTcB interval or are associated with an increased risk of torsades de pointes. (Appendix B)
5.1.14 . Careful rationalization of concomitant medications with the intent to discontinue or change to alternative medications if any concomitant medications are identified to be strong CYP3A4 inhibitors. (Appendix C)
5.1.15 Myeloablative or non-myeloablative allogeneic hematopoietic cell transplant.
Exclusion Criteria:5.2.1 Currently receiving or has received within 28 days of starting study drug nilotinib or any other tyrosine kinase inhibitor.
5.2.2 Received any anti-T or anti-B cell monoclonal antibody <= 28 days prior to the anticipated start of study drug.
5.2.3 Currently receiving > two immunosuppressants other than glucocorticoids.
5.2.4 Currently receiving a calcineurin inhibitor and sirolimus
5.2.5 Received any investigational agents <= 28 days before starting nilotinib.
5.2.6 Impaired cardiac function including any one of the following:
- Clinically significant resting brachycardia (<50 beats per minute).
- QTc > 450 msec on baseline ECG. If QTc >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
- Myocardial infarction within 12 months prior to starting study.
- Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension).
- History of or presence of clinically significant ventricular or atrial tachyarrhythmias. (including congenital long QT syndrome or a known family history of congenital long QT syndrome)
5.2.7 Allogeneic cell infusion within 100 days
5.2.8 Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines.
5.2.9 Progressive malignant disease including post transplant lymphoproliferative disease.
5.2.10 Any secondary malignancy except basal and squamous cell carcinoma of the skin within the past five years.
5.2.11 Nilotinib intolerance or hypersensitivity. 5.2.12 Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
5.2.13 Acute or chronic pancreatic disease 5.2.14 Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery.
5.2.15 Subject is pregnant, breast-feeding, or of childbearing potential without a negative serum or urine pregnancy test within 7 days of enrollment. Male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial.
5.2.16 Subject not willing to comply with treatment or response evaluation (including associated procedures such as skin biopsy).
5.2.17 Subject has a concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the patient.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Nilotinib
|
200, 400, 800, oral
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Frequency and severity of adverse events graded according to CTCAE v4.0
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Chronic GVHD response measured as change in physical exam and laboratory testing
Time Frame: baseline and 2 years
|
baseline and 2 years
|
Chronic GVHD response measured as change in daily corticosteroid requirement
Time Frame: baseline and 2 years
|
baseline and 2 years
|
Chronic GVHD response measured as frequency of treatment failure defined as discontinuation of study drug due to severe adverse effects or initiation of a new treatment for cGVHD
Time Frame: 2 years
|
2 years
|
Chronic GVHD response measured as change in cGVHD symptom burden
Time Frame: baseline and 2 years
|
baseline and 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: George Chen, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-18743 (Other Identifier: Stanford IRB)
- SU-06112010-6317 (Other Identifier: Stanford University)
- BMT222 (Other Identifier: OnCore)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lymphoma, Non-Hodgkin
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin LymphomaUnited States
-
Marker Therapeutics, Inc.RecruitingNon Hodgkin Lymphoma | Non-Hodgkin Lymphoma, Adult | Non-Hodgkin Lymphoma, Refractory | Non-Hodgkin Lymphoma, RelapsedUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell LymphomaUnited States
-
National Cancer Institute (NCI)RecruitingRefractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Primary Cutaneous... and other conditionsUnited States
-
Caribou Biosciences, Inc.RecruitingLymphoma | Lymphoma, Non-Hodgkin | B Cell Lymphoma | Non Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Relapsed Non Hodgkin Lymphoma | B Cell Non-Hodgkin's LymphomaUnited States, Australia, Israel
-
Mayo ClinicNot yet recruitingIndolent B-Cell Non-Hodgkin Lymphoma | Recurrent Indolent Non-Hodgkin Lymphoma | Refractory Indolent Non-Hodgkin Lymphoma | Recurrent Indolent B-Cell Non-Hodgkin Lymphoma | Refractory Indolent B-Cell Non-Hodgkin LymphomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingRefractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Hematopoietic Cell Transplantation RecipientUnited States
-
University of WashingtonRecruitingRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin LymphomaUnited States
-
Chongqing Precision Biotech Co., LtdRecruitingNon Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Relapsed Non-Hodgkin LymphomaChina
-
Estrella Biopharma, Inc.Eureka Therapeutics Inc.Not yet recruitingLymphoma | Lymphoma, Non-Hodgkin | Non-Hodgkin's Lymphoma | Non-Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | High-grade B-cell Lymphoma | CNS Lymphoma | Lymphomas Non-Hodgkin's B-Cell | Relapsed Non-Hodgkin Lymphoma | Lymphoma, Non-Hodgkins | Large B-Cell Lymphoma and other conditions
Clinical Trials on Nilotinib
-
Niguarda HospitalCompletedLeukemia, Myeloid, Chronic-PhaseItaly
-
Novartis PharmaceuticalsTerminatedPulmonary Arterial HypertensionSwitzerland, United States, Germany, Singapore, Korea, Republic of, Canada
-
Georgetown UniversityUnknownParkinson Disease | Parkinsons Disease With DementiaUnited States
-
XSpray MicroparticlesCompleted
-
Shenzhen Second People's HospitalDongguan People's Hospital; Zhongshan People's Hospital, Guangdong, China; The... and other collaboratorsRecruitingChronic Myeloid Leukemia, Chronic Phase | NilotinibChina
-
Andrew J. Wagner, MD, PhDMassachusetts General Hospital; Novartis; Brigham and Women's HospitalActive, not recruitingTenosynovial Giant Cell Tumor | Pigmented Villonodular Synovitis | Diffuse-type Giant Cell TumorUnited States
-
Novartis PharmaceuticalsNo longer availableHypereosinophilic Syndrome (HES)
-
KeifeRx, LLCWorldwide Clinical Trials; Life Molecular Imaging GmbH; Sun Pharmaceuticals Industries...Not yet recruiting
-
Novartis PharmaceuticalsNo longer availableAcute Lymphoblastic Leukemia (ALL)
-
Novartis PharmaceuticalsCompleted