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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00109707
Other study ID # CAMN107A2101
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date April 2005
Est. completion date September 2012

Study information

Verified date June 2021
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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)


Recruitment information / eligibility

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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Nilotinib


Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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, 

Outcome

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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