A Study of Oral Sapacitabine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia
- Registration Number
- NCT01303796
- Lead Sponsor
- Cyclacel Pharmaceuticals, Inc.
- Brief Summary
This Phase 3 study assesses two drug regimens as the initial treatment of patients who are at least 70 years of age and have newly diagnosed acute myeloid leukemia (AML) for whom the doctor does not recommend the use of standard intensive treatment or the patient has decided not to receive standard intensive treatment after being fully informed about its benefits and risks by his/her doctor. The two drug regimens are sapacitabine administered in alternating cycles with decitabine or decitabine alone. The purpose of the study is to learn which drug regimen is more likely to keep AML in check as long as possible.
- Detailed Description
This is a multicenter, randomized, Phase 3 study ("SEAMLESS") comparing two drug regimens (arms) as the front-line treatment of elderly patients aged 70 years or older with newly diagnosed acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy. In Arm A, sapacitabine is administered in alternating cycles with decitabine, and in Arm C decitabine is administered alone. The primary efficacy endpoint is overall survival. The study is designed to demonstrate an improvement in overall survival of Arm A versus Arm C.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 482
- Newly diagnosed AML based on WHO (World Health Organization) classification
- Age 70 years or older for whom the treatment of choice is low-intensity therapy by investigator assessment or who has refused intensive induction therapy recommended by investigator
- ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- Adequate renal function
- Adequate liver function
- Able to swallow capsules
- Agree to practice effective contraception
- Ability to understand and willingness to sign the informed consent form
- AML is of the sub-type of acute promyelocytic leukemia or extramedullary myeloid tumor without bone marrow involvement
- Having received any systemic anti-cancer therapy for AML or received treatment with hypomethylating agents or cytotoxic chemotherapy for preceding myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD)
- Known or suspected central nervous system (CNS) involvement by leukemia
- Uncontrolled intercurrent illness
- Known hypersensitivity to decitabine
- Known to be HIV-positive
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sapacitabine-decitabine alternating Decitabine Arm A sapacitabine administered in alternating cycles with decitabine Decitabine Decitabine Arm C Decitabine Sapacitabine-decitabine alternating Sapacitabine Arm A sapacitabine administered in alternating cycles with decitabine
- Primary Outcome Measures
Name Time Method Overall Survival up to 43 months The distribution of overall survival was estimated by the method of Kaplan and Meier. A log-rank analysis stratified by randomization stratification factors was used to compare overall survival between Arm A (decitabine/sapacitabine) versus Arm C (decitabine). Cox proportional hazards models were used to identify predictive factors for overall survival.
- Secondary Outcome Measures
Name Time Method Complete Remission With Incomplete Platelet Count Recovery (CRp) up to 43 months Normalization of bone marrow to \<=5% blasts; peripheral neutrophils \>=1000 /microliter, platelet \<=100,000 /microliter within 2 weeks of bone marrow biopsy/aspirate; independent of transfusions\*; and no extramedullary leukemia.
\*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response1-year Survival Percentage of patients alive at 1 year after randomization (participants were assessed up to 43 months for overall survival curve estimation but this measure presents the 1 year survival rate percentage). One-year survival is the percentage of patients who are alive at 1-year measured from the date of randomization.
Partial Remission (PR) up to 43 months Normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, \>=50% decrease in bone marrow blasts over pre-treatment but still \>5%; independent of transfusions\*
\*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the responseStable Disease (SD) up to 43 months Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks.
Complete Remission (CR) up to 43 months Normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, and bone marrow to \<=5 % blasts; independent of transfusions\*; and no extramedullary leukemia.
\* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the responseHematological Improvement up to 43 months HI with duration (HI)
1. Erythroid response (HI-E) for patients with pre-treatment hemoglobin \< 11 g/dL; Major response: \>2 g/dL increase in hemoglobin; for RBC, transfusion independence\* Minor response: 1 to 2 g/dL increase in hemoglobin; for RBC, a 50% decrease in transfusion requirements
2. Platelet response (HI-P) for pre-treatment platelet count \<100,000/mm3; Major response: an absolute increase of platelet count by \>=30,000/mm3; stabilization of platelet counts and platelet transfusion independence\* Minor response: \>=50% increase in platelet count with a net increase \> 10,000/mm3 but \<30,000/mm3
3. Neutrophil response (HI-N) for absolute neutrophil count (ANC) \< 1,500/mm3 before therapy; Major response: \>=100% increase, or an absolute increase of \>500/mm3, whichever is greater Minor response: \>=100% increase, but absolute increase \< 500/mm3
* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the responseBlood Products Transfused up to 43 months Number of units of packed red blood cells (PRBC) and/or platelet transfusions administered per 8-week period prior to the first dose of study drug and through the date of treatment discontinuation.
Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp) up to 43 months Duration of normalization of bone marrow to \<=5% blasts; peripheral neutrophils \>=1000 /microliter, platelet \<=100,000 /microliter within 2 weeks of bone marrow biopsy/aspirate; independent of transfusions\*; and no extramedullary leukemia.
\*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the responseDuration of Hematological Improvement (dHI) up to 43 months Duration of HI
1. Erythroid response (HI-E) for patients with pre-treatment hemoglobin \< 11 g/dL; Major response: \>2 g/dL increase in hemoglobin; for RBC, transfusion independence\* Minor response: 1 to 2 g/dL increase in hemoglobin; for RBC, a 50% decrease in transfusion requirements
2. Platelet response (HI-P) for pre-treatment platelet count \<100,000/mm3; Major response: an absolute increase of platelet count by \>=30,000/mm3; stabilization of platelet counts and platelet transfusion independence\* Minor response: \>=50% increase in platelet count with a net increase \> 10,000/mm3 but \<30,000/mm3
3. Neutrophil response (HI-N) for absolute neutrophil count (ANC) \< 1,500/mm3 before therapy; Major response: \>=100% increase, or an absolute increase of \>500/mm3, whichever is greater Minor response: \>=100% increase, but absolute increase \< 500/mm3
* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the responseDuration of Stable Disease (dSD) up to 43 months Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks.
Hospitalized Days up to 12 months In-patient days in hospital.
Duration of Partial Remission (dPR) up to 43 months Duration of normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, \>=50% decrease in bone marrow blasts over pre-treatment but still \>5%; independent of transfusions\*
\*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the responseDuration of Complete Remission (dCR) up to 43 months Durations of normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, and bone marrow to \<=5 % blasts; independent of transfusions\*; and no extramedullary leukemia.
\* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Trial Locations
- Locations (117)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
St. Francis Medical Group Oncology and Hematology Specialists
🇺🇸Indianapolis, Indiana, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
AOU Maggiore della Carità di Novara
🇮🇹Novara, Italy
AOOR Villa Sofia Cervello di Palermo
🇮🇹Palermo, Italy
Hopital St Louis Universite Paris 7
🇫🇷Paris, France
Universitaetsklinikum Charite Berlin, Campus Benjamin Franklin
🇩🇪Berlin, Germany
CHU de Strasbourg - Hopital Civil
🇫🇷Strasbourg, France
Uni. Napoli Ospedale Federico lI
🇮🇹Napoli, Italy
Inselspital Bern
🇨ðŸ‡Bern, Switzerland
University of Alabama Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
University of Maryland Greenbaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Shands Cancer Hospital at University of Florida
🇺🇸Gainesville, Florida, United States
UCLA Ronald Reagan Medical Center
🇺🇸Los Angeles, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Scripps Cancer Center
🇺🇸La Jolla, California, United States
Abramson Cancer Center of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Westchester Hematology Oncology Group, PC
🇺🇸Hawthorne, New York, United States
Cliniques Universitaires UCL de Mont-Godinne
🇧🇪Yvoir, Belgium
John Theurer Cancer Center at the Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Dartmouth - Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Univ. Klinik fur Innere Medizin III LKH
🇦🇹Salzburg, Austria
Centre Hospitalier De Jolimont-Lobbes
🇧🇪La Louviere, Belgium
CHRU De Montpellier Hopital St. Eloi
🇫🇷Montpellier, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Hospitalier d'Annecy
🇫🇷Pringy, France
CHU de Tours Hopital Bretonneau
🇫🇷Tours, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Petz Aladar Megyei Oktato Korhaz
ðŸ‡ðŸ‡ºGyÅ‘r, Hungary
Kaposi Mor Oktato Korhaz
ðŸ‡ðŸ‡ºKaposvár, Hungary
AOU Ospedali Riuniti Umberto I
🇮🇹Ancona, Italy
AO Ospedali Riuniti di Bergamo
🇮🇹Bergamo, Italy
AO Spedali Civili di Brescia
🇮🇹Brescia, Italy
PO Vito Fazzi
🇮🇹Lecce, Italy
AORN Antonio Cardarelli
🇮🇹Napoli, Italy
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario de Canarias
🇪🇸La Laguna, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Spain
Kings College Hospital and Guys and St Thomas' Hospital
🇬🇧London, United Kingdom
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States
St. Louis University Cancer Center
🇺🇸Saint Louis, Missouri, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Klinikum St. Georg
🇩🇪Leipzig, Germany
CHU de Lyon - Hopital Edouard Herriot
🇫🇷Lyon, France
Centre Hospitalier de la Cote Basque
🇫🇷Bayonne, France
Centre Hospitalier de Perigueux
🇫🇷Perigueux, France
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
SLK Kliniken Heilbronn
🇩🇪Heilbronn, Germany
Johannes Wesling Klinikum
🇩🇪Minden, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
TU Muenchen
🇩🇪Muenchen, Germany
Ospedale San Raffaele
🇮🇹Milano, Italy
Universita Cattolica del Sacro Cuore
🇮🇹Campobasso, Italy
AOU Careggi
🇮🇹Firenze, Italy
Universita di Bologna Ist Ematologia Oncologia Medica Seragnoli
🇮🇹Bologna, Italy
AOU San Luigi Gonzaga
🇮🇹Torino, Italy
University of Lodz N. Copernicus Memorial Hospital
🇵🇱Lodz, Poland
Wojewodzki Szpital Specjalistyczny
🇵🇱Legnica, Poland
Wojewódzki Szpital Specjalistyczny w Legnicy
🇵🇱Legnica, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 w Wroclawiu
🇵🇱Wroclaw, Poland
IHT Instytut Hematologii I Transfuzjologii w Warszawie
🇵🇱Warsaw, Poland
Hospital Universitari Germans Trias i Pujol ICO Badalona
🇪🇸Badalona, Spain
Hospital De La Santa Creu Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
ClÃnica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Son Espases
🇪🇸Palma de Mallorca, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico Universitario
🇪🇸Santiago de Compostela, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari "La Fe"
🇪🇸Valencia, Spain
Sunderby Hospital
🇸🇪Luleå, Sweden
Skåne Universitetssjukhus Univ Hospital Lund
🇸🇪Lund, Sweden
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Medizinische Universitaetsklinik
🇦🇹Innsbruck, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
AKH Wien
🇦🇹Wien, Austria
Ziekenhuis Netwerk Antwerpen Stuivenberg
🇧🇪Antwerpen, Belgium
AZ Sint-Jan Brugge-Oostende
🇧🇪Brugge, Belgium
CHU d'Amiens Hopital Sud
🇫🇷Amiens, France
Centre Hospitalier De Mulhouse
🇫🇷Mulhouse, France
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Universite Catholique de Louvain
🇧🇪Brussels, Belgium
Centre Hospitalier de Saint-Brieuc Yves Ie Foll
🇫🇷St Brieuc, France
Strasbourg Oncologie Liberale
🇫🇷Strasbourg, France
Policlinico San Matteo Di Pavia
🇮🇹Pavia, Italy
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Huntsman Cancer Institute at the University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Elisabethinen Krankenhaus
🇦🇹Linz, Austria
Krankenhaus der Barmherzigen Schwestern
🇦🇹Linz, Austria
Hanusch Krankenhaus
🇦🇹Wien, Austria
Klinikum Frankfurt Hoechst
🇩🇪Frankfurt, Germany
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Universitaetsklinikum Carl-Gustav-Carus Dresden
🇩🇪Dresden, Germany
St. Johannes Hospital
🇩🇪Duisburg, Germany
University of Debrecen
ðŸ‡ðŸ‡ºDebrecen, Hungary
AOU San Martino IST
🇮🇹Genova, Italy
Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku
🇵🇱Gdansk, Poland