Acute Myeloid Leukemia Clinical Trial
— ACEOfficial title:
Phase 2 Open-Label, AC220 Monotherapy Efficacy (ACE) Study in Patients With Acute Myeloid Leukemia (AML) With and Without FLT3-ITD Activating Mutations
Verified date | December 2019 |
Source | Daiichi Sankyo, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without any rest periods, until disease progression, relapse, intolerance to the drug, or elective allogeneic hematopoietic stem cell transplantation (HSCT).
Status | Completed |
Enrollment | 333 |
Est. completion date | December 31, 2014 |
Est. primary completion date | September 28, 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility |
Current enrollment is open only to FLT3-ITD positive, Cohort 1. Inclusion Criteria: 1. Males and females age =18 years in second relapse or refractory. 2. Males and females age =60 years in first relapse or refractory. 3. Must have baseline bone marrow sample taken. 4. Morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS with =20% bone marrow or peripheral blasts), as defined by the World Health Organization (WHO) criteria, confirmed by pathology review at treating institution. 5. Able to swallow the liquid study drug. 6. Eastern Cooperative Oncology Group performance status of 0 to 2 7. In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. The use of chemotherapeutic or antileukemic agents other than hydroxyurea is not permitted during the study with the possible exception of intrathecal (IT) therapy at the discretion of the Investigator and with the agreement of the Sponsor. 8. Persistent chronic clinically significant non-hematological toxicities from prior treatment must be =Grade 1. 9. Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220. 10. Serum creatinine =1.5 × upper limit of normal (ULN) and glomerular filtration rate (GFR) > 30 mL/min 11. Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits. 12. Total serum bilirubin =1.5 × ULN 13. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =2.5 × ULN 14. Females of childbearing potential must have a negative pregnancy test (urine ß-hCG). 15. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study. 16. Written informed consent must be provided. Exclusion Criteria: 1. Patients over the age of 85 years except at the discretion of the Investigator and with agreement of the Sponsor. 2. Diagnosis of acute promyelocytic leukemia 3. Diagnosis of chronic myelogenous leukemia (CML) in blast crisis 4. AML in relapse or refractory after 3 or more previous lines of chemotherapy (and/or HSCT) treatment 5. AML or antecedent MDS secondary to prior chemotherapy 6. Persistent clinically significant non-hematological toxicity that is Grade >1 by NCI CTCAE v4 from prior chemotherapy 7. Patients who have had HSCT and are within 100 days of transplant and/or are still taking immunosuppressive drugs and/or have clinically significant graft-versus-host disease requiring treatment and/or have >Grade 1 persistent non hematological toxicity related to the transplant 8. Clinically active central nervous system (CNS) leukemia. Patients with CNS leukemia, which is controlled, but who are still receiving IT therapy at study entry may be considered eligible and continue receive IT therapy at the discretion of the Investigator and with agreement of the Sponsor. 9. Patients who have previously received AC220 10. Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment) 11. Major surgery within 4 weeks prior to enrollment in the study 12. Radiation therapy within 4 weeks prior to, or concurrent with study 13. Use of concomitant drugs that prolong the time between the start of the Q wave and the end of the T wave (QT)/corrected interval between the Q wave and T wave (QTc) interval and/or are CYP3A4 inhibitors are prohibited with the exception of antibiotics, antifungals, and other antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. 14. Uncontrolled or significant cardiovascular disease 15. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential 16. Men who are unwilling to use contraception if their partners are of childbearing potential 17. Active, uncontrolled infection 18. Human immunodeficiency virus positivity 19. Active hepatitis B or C or other active liver disease 20. History of cancer, except Stage 1 cervix or nonmelanotic skin cancer, with the possible exception of patients in complete remission |
Country | Name | City | State |
---|---|---|---|
Canada | Princess Margaret Hospital | Toronto | Ontario |
France | Hopital Avicenne | Bobigny | |
France | Centre Hospitalier Universitaire d'Angers | d'Angers | |
France | Centre Hospitalier Universitaire Grenoble | Grenoble | |
France | Centre Hospitalier de Versailles | Le Chesnay | |
France | Hopital Claude Huriez | Lille | |
France | Centre Hospitalier Universitaire Limoges | Limoges | |
France | Hopital Edouard Herriot | Lyon | |
France | Institut Paoli Calmettes Centre Regional de Lutte Contre le Cancer | Marseille | Cedex 9 |
France | Hopital Saint-Antoine | Paris | |
France | Hopital Saint-Louis | Paris | |
France | Hopital Haut-Leveque | Pessac | |
France | Centre Henry Becquerel, Service d'Hematologie | Rouen | |
France | Centre Hospitalier Regional Universitaire, Hopital de Hautepierre | Strasbourg | |
France | Hematologie - CHU Purpan | Toulouse | Cedex |
France | Centre Hospitalier Universitaire Brabois | Vandoeuvre les Nancy | |
Germany | Charite Campus Virchow Klinikum | Berlin | |
Germany | Charite, Campus Benjamin Franklin | Berlin | |
Germany | Universitatsklinikum Bonn | Bonn | |
Germany | Unikliniksklinikum Carl Gustav Carus | Dresden | |
Germany | Uniklinik Essen, Westdeutsches Tumorzentrum | Essen | |
Germany | Klinikum der Johann Wolfgang Goethe Universitat | Frankfurt am Main | |
Germany | Asklepios Klinik St Georg | Hamburg | |
Germany | Medizinische Hochschule Hannover | Hannover | |
Germany | Universitatsklinikum Heidelberg | Heidelberg | |
Germany | Universitatsklinikum Jena | Jena | |
Germany | Universitatsklinikum Leipzig Selbstandige Abteilung fur Hamatologie | Leipzig | |
Germany | Universitatsklinikum Magdeburg | Magdeburg | |
Germany | Universitatsklinikum Mannheim | Mannheim | |
Germany | Philipps-Universitat Marburg | Marburg | |
Germany | Klinikum rechts der Isar, Technische Universitat Munchen | Munchen | |
Germany | Universitatsklinikum Munster | Munster | |
Germany | Universitatsklinikum Regensburg Abteilung fur Hamatologie | Regensburg | |
Germany | Robert-Bosch-Krankenhaus GmbH | Stuttgart | |
Germany | Universitatsklinikum Tubingen | Tubingen | |
Germany | Universitatsklinikum Ulm | Ulm | |
Germany | Universitatsklinikum Wurzburg | Wurzburg | |
Italy | Instituto Di Ematologia "L.Ea. Seragnoli" | Bologna | |
Italy | Unita Trapianti di Midollo Osseo per Adulti | Brescia | |
Italy | Presidio Ospedaliero "A. Businco" - Centro di Riferimento Oncologico Regionale | Cagliari | |
Italy | Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto | Catania | |
Italy | Azienda Ospedaliera Universitaria San Martino | Genova | |
Italy | Farmacia Ospidaliera | Orbassano | |
Italy | Ospedale Civile S. Maria delle Croci | Ravenna | |
Italy | Ospedale Sant Eugenio | Roma | |
Italy | Universita Degli Studi di Roma Tor Vergata | Roma | |
Italy | Azienda Ospedaliero Universitaria Senese | Siena | |
Italy | Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine, Clinica Ematologica | Udine | |
Netherlands | University Medical Center Groningen | Groningen | |
Netherlands | Utrecht University Medical Centre, Dept. of Hematology | Utrecht | |
Poland | Dolnoslaskie Centrum Transplantacji Komorkowych z | Wroclaw | |
Spain | Hospital Clinic i Provincial de Barcelona | Barcelona | |
Spain | Hospital de la Santa Creu i Sant Pau | Barcelona | |
Spain | Institut Catala d'Oncologia del Hospital Universitari Germans | Barcelona | |
Spain | Instituto Catalan de Oncologia-Hospital Universitari de Girona | Girona | |
Spain | Hospital de la Princesa, Servicio de Hematologia | Madrid | |
Spain | Hospital General Universitario Gregorio Maranon | Madrid | |
Spain | Clinica Universidad de Navarra | Pamplona | Navarra |
Spain | Hospital Universitario de Salamanca, Hospital Clinico, Servicio de Hematologia | Salamanca | |
Spain | Hospital La Fe, Servicio de Hematologia | Valencia | |
United Kingdom | Addenbrook's Hospital | Cambridge | |
United Kingdom | Castle Hill Hospital | Cottingham | |
United Kingdom | Saint James University Hospital, Institute of Oncology | Leeds | |
United Kingdom | Hanmmersmith Hospital, Dept. of Hematology | London | |
United Kingdom | Nottingham University Hospitals NHS Trust | Nottingham | |
United States | University of Michigan Medical Center | Ann Arbor | Michigan |
United States | Johns Hopkins Hospital | Baltimore | Maryland |
United States | University of Maryland | Baltimore | Maryland |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | Northwestern Memorial Hospital | Chicago | Illinois |
United States | Rush University Medical Center | Chicago | Illinois |
United States | Karmanos Cancer Institute | Detroit | Michigan |
United States | Milton S. Hershey Medical Center | Hershey | Pennsylvania |
United States | M.D. Anderson Cancer Center | Houston | Texas |
United States | Indiana University | Indianapolis | Indiana |
United States | University of Iowa Hospitals and Clinics | Iowa City | Iowa |
United States | University of Wisconsin Hospital and Clinics | Madison | Wisconsin |
United States | Clinical Trials Center | Nashville | Tennessee |
United States | The Vanderbuilt Clinic | Nashville | Tennessee |
United States | Columbia University | New York | New York |
United States | Abramson Cancer Center | Philadelphia | Pennsylvania |
United States | Oregon Health and Science University | Portland | Oregon |
United States | Mayo Clinic | Rochester | Minnesota |
United States | University of California, San Francisco | San Francisco | California |
United States | Seattle Cancer Care Alliance | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Daiichi Sankyo, Inc. |
United States, Canada, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD[+] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia <1 x 10^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission. |
Within the first 3 cycles of treatment (84 days) | |
Primary | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD[-] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia <1 x 10^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission. |
Within the first 3 cycles of treatment (84 days) | |
Primary | Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status | CRc is defined as composite complete remission (CR+CRp+CRi) - CR = complete remission; CRp = complete remission with incomplete platelet recovery; CRi = complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia = all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia <1 x 10^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib = all criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion. | within 28 months | |
Secondary | Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data | Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of >1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria. |
From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment | |
Secondary | Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data | Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of >1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria. |
From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment | |
Secondary | Duration of Any Response in FLT3-ITD (+) Participants | Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population). | From the time of any response until disease progression or death, up to approximately 3 years post treatment | |
Secondary | Duration of Any Response in FLT3-ITD (-) Participants | Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population). | From the time of any response until disease progression or death, up to approximately 3 years post treatment | |
Secondary | Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants | Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population). | From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment | |
Secondary | Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants | Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population). | From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment | |
Secondary | Median Duration of Overall Survival in FLT3-ITD (+) Participants | Kaplan-Meier analysis of overall survival (Safety Population) | Time from first dose to death from any cause, up to 3 years post treatment | |
Secondary | Median Duration of Overall Survival in FLT3-ITD (-) Participants | Kaplan-Meier analysis of overall survival (Safety Population) | Time from first dose to death from any cause, up to approximately 3 years post treatment | |
Secondary | Early Treatment-related Death | Early treatment-related deaths included all treatment-related deaths prior to the end of Cycle 3 with a 3-day window (Cycle 3 end date + 3 days), unless the death was following a CRc response assessed by the Investigator. | Within first 3 cycles of treatment (84 days) |
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