A Multicenter Phase I/II Study of the Prophylactic Inhibition of BCR-ABL Tyrosine Kinase by Tasigna ® (Nilotinib) After Hematopoietic Cell Transplantation for Philadelphia Chromosome-Positive Leukemias.
I. To determine the safety of the administration of nilotinib between Day 81 and Day 365
after hematopoietic cell transplantation (HCT) in patients with Philadelphia chromosome
positive (Ph+) leukemia.
I. To quantify the breakpoint cluster region (BCR)/Abelson murine leukemia (ABL) transcript
load after HCT during tyrosine kinase inhibitor therapy in patients with Ph+ leukemia
treated sequentially with imatinib (imatinib mesylate) and nilotinib from the time of
II. To evaluate survival at 1 year in patients with Ph+ leukemia who received sequential
imatinib and nilotinib from the time of engraftment.
III. To determine if imatinib can be co-administered with nilotinib for patients with rising
levels of BCR/ABL on 2 consecutive occasions after HCT.
IV. To confirm that imatinib can be delivered at an average daily dose of 400 mg at least
85% of the time in the majority of adults during the first 80 days after HCT.
V. To determine whether nilotinib can be administered safely at a daily dose of at least 300
mg (175 mg/m^2 in children < 17 years) at least 70% of the time to patients with imatinib
resistant Ph+ leukemia during the first 80 days after HCT.
VI. To determine treatment efficacy success at 1 year post-transplant as demonstrated by
complete hematological remission, absence of Philadelphia chromosome, and not satisfying any
of the criteria for treatment failure.
Beginning after engraftment and blood counts recover (21-28 days after allogeneic stem cell
transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate orally (PO)
once daily (QD) until day 80 and then nilotinib PO twice daily (BID) on days 81-445.
Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after
engraftment and blood counts recover until day 445.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability of nilotinib therapy in patients with imatinib-sensitive leukemia graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0
Treatment safety failure is defined for patients with imatinib sensitive Ph+ leukemia as the inability to be able to deliver at least 400 milligrams per day of nilotinib in adults, and 230 milligrams/m2 per day in children, for at least 85% of the time interval between 81 and 365 days after transplant because of toxicity.
Up to 365 days post-transplant
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|Oregon Health and Science University||Portland, Oregon 97201|
|Stanford University Hospitals and Clinics||Stanford, California 94305|
|H Lee Moffitt Cancer Center and Research Institute Phase 2 Consortium||Tampa, Florida 33612|