Chronic Myelogenous Leukemia Clinical Trial
Official title:
A Phase IA/II Multicenter, Dose-escalation Study of Oral AMN107 on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant/Intolerant CML in Chronic or Accelerated Phase or Blast Crisis, Relapsed/Refractory Ph+ ALL, and Other Hematologic Malignancies.
Verified date | June 2021 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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)
Status | Completed |
Enrollment | 507 |
Est. completion date | September 2012 |
Est. primary completion date | September 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: Main inclusion criteria include: - Patients with CML in blast crisis, CML in accelerated phase defined as never in blast crisis phase, or CML in chronic phase defined as never been in blast crisis phase or accelerated phase who have: *developed progressive disease during therapy with at least 600 mg of imatinib per day, -OR- *patients with CML on imatinib therapy, at any dose, developing progressive disease and the presence of a genetic mutation likely to result in imatinib resistance -OR- *have developed an intolerance to imatinib - Relapsed or refractory Ph+ ALL - Hypereosinophilic syndrome/chronic eosinophilic leukemia. - Systemic mastocytosis who have a clinical indication for treatment. - Prior imatinib therapy for patients with Ph+ ALL, HES/CEL and SM is permitted but is not required - CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible - Written informed consent prior to any study procedures being performed Exclusion Criteria: - Impaired cardiac function - Patients with severe/chronic or uncontrolled medical conditions (including but not limited to diabetes, infections, GI impairment, CNS infiltration, liver and kidney disease) - Prior and concomitant use of certain medications (including but not limited to warfarin, chemotherapy, hematopoietic colony-stimulating growth factors, medications that can affect electrocardiogram test results, other investigational drugs ) - Women who are pregnant or breastfeeding - Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention. - Patients unwilling to comply with the protocol. - Known diagnosis of human immunodeficiency virus (HIV) infection Other protocol-defined inclusion/exclusion criteria may apply |
Country | Name | City | State |
---|---|---|---|
Australia | Novartis Investigative Site | Adelaide | South Australia |
Australia | Novartis Investigative Site | Prahran | Victoria |
Australia | Novartis Investigative Site | St. Leonards | New South Wales |
Austria | Novartis Investigative Site | Wien | |
Belgium | Novartis Investigative Site | Bruxelles | |
Belgium | Novartis Investigative Site | Haine-saint-Paul | |
Belgium | Novartis Investigative Site | Leuven | |
Belgium | Novartis Investigative Site | Yvoir | |
Canada | Novartis Investigative Site | Montreal | Quebec |
Canada | Novartis Investigative Site | Montreal | Quebec |
Canada | Novartis Investigative Site | Toronto | Ontario |
Canada | Novartis Investigative Site | Vancouver | British Columbia |
Denmark | Novartis Investigative Site | Vejle | |
Finland | Novartis Investigative Site | HUS Helsinki | |
France | Novartis Investigative Site | Bordeaux Cedex | |
France | Novartis Investigative Site | Créteil | |
France | Novartis Investigative Site | Dijon | |
France | Novartis Investigative Site | Lille | |
France | Novartis Investigative Site | Limoges cedex | |
France | Novartis Investigative Site | Lyon | |
France | Novartis Investigative Site | Marseille | |
France | Novartis Investigative Site | Poitiers | |
France | Novartis Investigative Site | Rennes | |
France | Novartis Investigative Site | Vandoeuvre les Nancy | |
Germany | Novartis Investigative Site | Berlin | |
Germany | Novartis Investigative Site | Duesseldorf | |
Germany | Novartis Investigative Site | Frankfurt/M | |
Germany | Novartis Investigative Site | Hamburg | |
Germany | Novartis Investigative Site | Leipzig | |
Germany | Novartis Investigative Site | Mainz | |
Germany | Novartis Investigative Site | Mannheim | |
Germany | Novartis Investigative Site | Muenchen | |
Hong Kong | Novartis Investigative Site | Pokfulam | |
Italy | Novartis Investigative Site | Bergamo | BG |
Italy | Novartis Investigative Site | Bologna | BO |
Italy | Novartis Investigative Site | Genova | GE |
Italy | Novartis Investigative Site | Milano | MI |
Italy | Novartis Investigative Site | Monza | MB |
Italy | Novartis Investigative Site | Napoli | |
Italy | Novartis Investigative Site | Orbassano | TO |
Italy | Novartis Investigative Site | Pavia | PV |
Italy | Novartis Investigative Site | Pescara | PE |
Italy | Novartis Investigative Site | Reggio Calabria | RC |
Italy | Novartis Investigative Site | Roma | RM |
Italy | Novartis Investigative Site | Roma | RM |
Italy | Novartis Investigative Site | Roma | RM |
Korea, Republic of | Novartis Investigative Site | Hwasun-gun | Jeollanam-do |
Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
Korea, Republic of | Novartis Investigative Site | Taegu | |
Netherlands | Novartis Investigative Site | Amsterdam | |
Netherlands | Novartis Investigative Site | Rotterdam | |
New Zealand | Novartis Investigative Site | Grafton | Auckland |
Norway | Novartis Investigative Site | Oslo | |
Poland | Novartis Investigative Site | Katowice | |
Poland | Novartis Investigative Site | Lodz | |
Poland | Novartis Investigative Site | Warszawa | |
Poland | Novartis Investigative Site | Warszawa | |
Poland | Novartis Investigative Site | Wroclaw | |
Singapore | Novartis Investigative Site | Singapore | |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | Hospitalet de LLobregat | Catalunya |
Sweden | Novartis Investigative Site | Göteborg | |
Sweden | Novartis Investigative Site | Linköping | |
Sweden | Novartis Investigative Site | Lund | |
Sweden | Novartis Investigative Site | Uppsala | |
Switzerland | Novartis Investigative Site | Basel | |
Switzerland | Novartis Investigative Site | Genève | |
Taiwan | Novartis Investigative Site | Niaosong Township | |
United Kingdom | Novartis Investigative Site | Birmingham | |
United Kingdom | Novartis Investigative Site | Cambridge | |
United Kingdom | Novartis Investigative Site | Glasgow - Scotland | |
United Kingdom | Novartis Investigative Site | Leeds | |
United Kingdom | Novartis Investigative Site | Liverpool | |
United Kingdom | Novartis Investigative Site | London | |
United Kingdom | Novartis Investigative Site | London | |
United Kingdom | Novartis Investigative Site | Newcastle upon Tyne | |
United States | University of Michigan Health System Clinical Trials Office | Ann Arbor | Michigan |
United States | University of Colorado Hospital | Aurora | Colorado |
United States | Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie | Baltimore | Maryland |
United States | Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2) | Beech Grove | Indiana |
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Roswell Park Cancer Institute Rosewell SC | Buffalo | New York |
United States | University of Chicago Medical Center Dept. of U. of Chicago Hosp(3) | Chicago | Illinois |
United States | University of Illinois at Chicago Divisionof Hematology/Oncology | Chicago | Illinois |
United States | Wayne State University | Detroit | Michigan |
United States | City of Hope National Medical Center | Duarte | California |
United States | Duke University Medical Center | Durham | North Carolina |
United States | The Jones Clinic | Germantown | Tennessee |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | MD Anderson Cancer Center/University of Texas | Houston | Texas |
United States | Vanderbilt University Medical Center, Clinical Trials Center Investigational Drug Services | Nashville | Tennessee |
United States | Ochsner Clinic Foundation | New Orleans | Louisiana |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Oregon Health Sciences University | Portland | Oregon |
United States | Mayo Clinic - Rochester | Rochester | Minnesota |
United States | University of Rochester Medical Center | Rochester | New York |
United States | Swedish Cancer Institute | Seattle | Washington |
United States | Stanford University Medical Center | Stanford | California |
United States | H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt | Tampa | Florida |
United States | Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Hong Kong, Italy, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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). | Up to End of the Treatment (Approximately 7.5 years) | |
Primary | 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. |
Up to End of the Treatment (Approximately 7.5 years) | |
Secondary | 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). | Up to End of the Treatment (Approximately 7.5 years) | |
Secondary | 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. | Up to End of the Treatment (Approximately 7.5 years) | |
Secondary | 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. | Up to End of the Treatment (Approximately 7.5 years) | |
Secondary | 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). |
Up to End of the Treatment (Approximately 7.5 years) | |
Secondary | 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. | Up to End of the Treatment (Approximately 7.5 years) | |
Secondary | 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. | From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) |
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