The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions: Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1) Group A - Imatinib failure only (arms 2, 3 and 4) * imatinib-resistant or intolerant CML - Chronic Phase (CP) * imatinib-resistant or intolerant CML - Accelerated Phase (AP) * imatinib-resistant or intolerant CML - Blast Crisis (BC) Group B - Imatinib and other TKI failure (arms 2, 3 and 4) * imatinib-resistant or intolerant CML - Chronic Phase (CP) * imatinib-resistant or intolerant CML - Accelerated Phase (AP) * imatinib-resistant or intolerant CML - Blast Crisis (BC) Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5) Systemic mastocytosis (Sm) (arm 6)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
507
City of Hope National Medical Center
Duarte, California, United States
Stanford University Medical Center
Stanford, California, United States
University of Colorado Hospital
Aurora, Colorado, United States
H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt
Tampa, Florida, United States
University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)
Chicago, Illinois, United States
Number of Participants With Major Cytogenetic Response (MCyR)
Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Number of Participants Confirmed Overall Hematological Response (Phase II)
Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes \< 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver). Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Number of Participants With Overall Major Cytogenetic Responses (Phase II)
Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and \>0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Number of Participants With Complete Hematologic Response (Phase II)
A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; \< 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Participants With (MMR) Major Molecular Response (Phase II)
MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Time to Progression (TTP) (Phase II)
Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death. Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Overall Survival (OS) (Phase II)
OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.
Time frame: Up to End of the Treatment (Approximately 7.5 years)
Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time frame: From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)
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University of Illinois at Chicago Divisionof Hematology/Oncology
Chicago, Illinois, United States
Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2)
Beech Grove, Indiana, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
...and 91 more locations