Phase 1 Nilotinib in Steroid Dependent/Refractory Chronic Graft Versus Host Disease

NCT01155817 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-18743SU-06112010-6317BMT222
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Bone Marrow Transplant Failure; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Peripheral

Outcome Measures

Primary Outcomes (1)

• Frequency and severity of adverse events graded according to CTCAE v4.0

  2 years

Secondary Outcomes (4)

• Chronic GVHD response measured as change in physical exam and laboratory testing

  baseline and 2 years

• Chronic GVHD response measured as change in daily corticosteroid requirement

  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

  2 years

• Chronic GVHD response measured as change in cGVHD symptom burden

  baseline and 2 years

Study Arms (1)

Nilotinib

EXPERIMENTAL

Drug: Nilotinib

Interventions

Nilotinib DRUG

200, 400, 800, oral

Also known as: Tasigna, AMN107

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Any previous treatments for cGVHD (except nilotinib). Participants may have received nilotinib for other reasons besides cGVHD such as leukemia or solid tumor.
• 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.
• 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.
• 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
• \>= 18 years old
• Life expectancy \>= 6 months.
• 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).
• Laboratory parameters:
• Creatinine \< 1.5 x ULN
• ANC \> 1.5 x 10\^9/L

You may not qualify if:

• Received any anti-T or anti-B cell monoclonal antibody \<= 28 days prior to the anticipated start of study drug.
• Currently receiving \> two immunosuppressants other than glucocorticoids.
• Currently receiving a calcineurin inhibitor and sirolimus
• Received any investigational agents \<= 28 days before starting nilotinib.
• 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)
• Allogeneic cell infusion within 100 days
• Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines.
• Progressive malignant disease including post transplant lymphoproliferative disease.
• Any secondary malignancy except basal and squamous cell carcinoma of the skin within the past five years.
• 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).

Sponsors & Collaborators

• Stanford University: lead
• Novartis: collaborator

Study Sites (5)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Gordon and Leslie Diamond Health Care Centre Hematology Administration

Vancouver, British Columbia, V5Z1M9, Canada

Location

Related Publications (1)

• Chen GL, Carpenter PA, Broady R, Gregory TK, Johnston LJ, Storer BE, Beumer JH, Qiu J, Cerda K, Le R, Otani JM, Liu H, Ross MA, Arai S, Flowers MED, McCarthy PL, Miklos DB. Anti-Platelet-Derived Growth Factor Receptor Alpha Chain Antibodies Predict for Response to Nilotinib in Steroid-Refractory or -Dependent Chronic Graft-Versus-Host Disease. Biol Blood Marrow Transplant. 2018 Feb;24(2):373-380. doi: 10.1016/j.bbmt.2017.10.021. Epub 2017 Oct 16.

  PMID: 29051021 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Peripheral

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell

Study Officials

• David Miklos

  Stanford University

  PRINCIPAL INVESTIGATOR

• George Chen

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: June 15, 2010
• First Posted: July 2, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 15, 2020

Record last verified: 2020-04

Locations

US (4); CA (1)