9L-14-3: A Phase 4 Safety And Efficacy Study Of Bosutinib (Bosulif) In Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated With One Or More Tyrosine Kinase Inhibitors
The study drug, bosutinib is a tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia chromosome positive chronic phase chronic myelogenous leukemia (CML) previously treated with other TKI therapy. CML is the fourth most commonly occurring adult leukemia. The transformation of CML from a deadly cancer to a chronic illness that took place over the last decade has been to the development of TKIs (inhibitors of the kinase activity of BCR-ABL1). The purpose of this phase 4 study is to fulfill the post-authorization commitment made by Pfizer to the European Medicines Agency in providing additional safety and efficacy data in approximately 150 Ph+ CML patients with high unmet medical need, including 75 chronic phase (CP), accelerated phase( AP) or BP(blastic phase) participants in the 4th or later line treatment setting. The primary objectives of this study are to estimate the 1-year (Week 52) probability of cumulative Major Cytogenetic Response (MCyR) in CP Ph+ CML patients with 1 or 2 prior lines of TKI therapy or 3 or more prior lines of TKI therapy. And to estimate the 1-year (Week 52) probability of cumulative confirmed Overall Hematological Response (OHR) in AP and BP Ph+ CML patients with any prior TKI therapy.This is a single-arm, open-label, non-randomized, multi-center Phase 4 study to evaluate bosutinib (Bosulif ) in patients with CP/AP/BP Ph+ CML whose disease has failed prior treatment with commercially available TKIs due to drug resistance or intolerance, or are otherwise contraindicated for treatment with commercially available TKIs such as imatinib, dasatinib, or nilotinib.Participants will receive bosutinib for at least 4 years from the time of first dose. Participants discontinuing bosutinib before completing at least 4 years of therapy will be followed for survival until they complete at least 4 years on study. Participants completing at least 4 years of bosutinib with continued benefit may be switched to commercially available therapy at that time. During the first 3 months of study, disease assessments will be performed weekly during the first month, then approximately every 4 weeks until Week 13. Assessments will then be performed every 3 months until Week 52, then at 6 month intervals during year 2, 3, and 4 of treatment.This study does not include any formal sample size determination. All treated Ph+ participants will be included in the efficacy analyses. Analyses will be presented by disease stage and/or line of therapy. The exploratory time-to-event endpoints of OS and PFS will be summarized using the Kaplan-Meier method or by cumulative incidence, whichever is more appropriate.
SWOG-1318 A Phase II Study of Blinatumomab (NSC-765986) and POMP (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) for Patients >/= 65 Years of Age with Newly Diagnosed Philadelphia-Chromosome Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) and of Dasatinib (NSC-732517), Prednisone and Blinatumomab for Patients >/= 65 Years of Age with Newly Diagnosed Philadelphia-Chromosome Positive (Ph+) ALL
I. To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia
(Ph)-negative acute lymphoblastic leukemia (ALL) treated with blinatumomab followed by POMP
(prednisone, vincristine sulfate, methotrexate, and mercaptopurine) maintenance.
II. To evaluate in a preliminary manner (feasibility study) the safety of dasatinib-steroid
based induction followed by blinatumomab treatment in combination with dasatinib followed by
dasatinib-based maintenance in patients with newly diagnosed Ph-positive ALL,
relapsed/refractory Ph-positive ALL, and Ph-like dasatinib-sensitive mutations or kinase
fusions (DSMKF) ALL (newly-diagnosed relapsed or refractory).
I. To evaluate toxicities in these patient populations treated with these regimens.
II. To estimate the rates of complete response (CR), complete remission with incomplete count
recovery (CRi) and disease-free survival in Ph-negative patients.
III. To estimate disease-free and overall survival in Ph-positive ALL and Ph-like DSMKF ALL.
IV. To estimate in each cohort the rate of minimal residual disease (MRD) negativity, and the
time to achieve MRD negativity (exploratory analysis).
V. To determine whether anti-idiotype antibodies directed against blinatumomab develop with
blinatumomab treatment in this study.
OUTLINE: Patients are assigned to 1 of 2 treatment cohorts according to Philadelphia
COHORT I (PHILADELPHIA CHROMOSOME NEGATIVE PATIENTS):
INDUCTION: Patients receive blinatumomab intravenously (IV) continuously over 24 hours on
days 1-28. Treatment repeats every 42 days for 2 courses in the absence of disease
progression or unacceptable toxicity.
RE-INDUCTION: Patients not achieving CR or CRi after Induction, receive blinatumomab IV
continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable
POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28.
Treatment repeats every 42 days for 3 courses in the absence of disease progression or
MAINTENANCE: Patients receive prednisone orally (PO) on days 1-5, vincristine sulfate IV on
day 1, mercaptopurine PO on days 1-28, and methotrexate PO on days 1, 8, 15, and 22.
Treatment repeats every 28 days for 18 courses in the absence of disease progression or
COHORT II (PHILADELPHIA CHROMOSOME POSITIVE PATIENTS):
INDUCTION: Patients receive dasatinib PO twice daily (BID) on days 1-84 and prednisone PO on
days 1-24 with tapering on days 25-32 in the absence of disease progression or unacceptable
RE-INDUCTION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28.
Treatment repeats every 42 days for 2 courses in the absence of disease progression or
POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28 and
dasatinib PO once daily (QD) on days 1-42. Treatment repeats every 42 days for 3 courses in
the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive dasatinib PO BID on days 1-28 and prednisone PO on days 1-5.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 2 years, and then annually until 10 years from initial registration.
9L-13-1: Correlative Biomarker Study for MPD-RC Treatment Studies in the Philadelphia Chromosome Negative Myeloproliferative Neoplasms (MPN)
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are clonal hematopoietic malignancies originating at the level of the pluripotent hematopoietic stem cell. MPNs have the potential to undergo clonal evolution and a stepwise progression that terminates in bone marrow failure due to myelofibrosis, ineffective hematopoiesis, or in transformation to acute leukemia. Recently it has been learned that a point mutation in the tyrosine kinase, Jak2, accounts for the characteristic growth factor hypersensitivity observed in MPNs, however, the molecular mechanisms that result in the etiology and progression of these neoplasms have not been fully characterized. Because of the long evolution of these neoplasms, identifying biomarkers of disease progression and the development of molecularly targeted translational therapies has been difficult.The principal objective of this study is to collect and store tissue samples from patients with myeloproliferative neoplasms (PV, PMF, and ET). Tissue samples will be used to perform a variety of biomarker studies to monitor the effects of a particular therapeutic intervention. The specimens will be obtained from study participants either at the time of diagnosis, remission, or at relapse, or other specific time points as specified by the individual treatment/research protocols.Study participants qualify to take part in this research study because they have agreed to participate in an MPD-RC treatment study for which this biomarker study is a mandatory component. Participants will be asked to participate in this study that allows for the storage of a small portion of the participants blood and bone marrow and toenail clippings for research. This study is being conducted by the Myeloproliferative Disorders Research Consortium (MPD-RC) through a grant provided by the National Cancer Institute (NCI). These samples will be frozen and securely stored at the MPD-RC Research Laboratory at the New York Blood Center in New York, New York. Participation in this study is expected to last from 2 to 4 years.