Clinical trial NCT01303796: A Study of Oral Sapacitabine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia
Official title: A Phase III Randomized Study of Oral Sapacitabine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: AML
Lead sponsor: Cyclacel Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-02-25
Enrollment: 482
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Overall Survival
timeFrame: up to 43 months
Secondary outcomes:
measure: Complete Remission (CR)
timeFrame: up to 43 months
measure: Complete Remission With Incomplete Platelet Count Recovery (CRp)
timeFrame: up to 43 months
measure: Partial Remission (PR)
timeFrame: up to 43 months
measure: Hematological Improvement
timeFrame: up to 43 months
measure: Stable Disease (SD)
timeFrame: up to 43 months
measure: Blood Products Transfused
timeFrame: up to 43 months
measure: Hospitalized Days
timeFrame: up to 12 months
measure: 1-year Survival
timeFrame: 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).
measure: Duration of Complete Remission (dCR)
timeFrame: up to 43 months
measure: Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp)
timeFrame: up to 43 months
measure: Duration of Partial Remission (dPR)
timeFrame: up to 43 months
measure: Duration of Hematological Improvement (dHI)
timeFrame: up to 43 months
measure: Duration of Stable Disease (dSD)
timeFrame: up to 43 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Gainesville
country: United States
facility: Shands Cancer Hospital at University of Florida
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: St. Francis Medical Group Oncology and Hematology Specialists
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Greenbaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth - Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: John Theurer Cancer Center at the Hackensack University Medical Center
state: New Jersey
city: Hawthorne
country: United States
facility: Westchester Hematology Oncology Group, PC
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at the University of Utah
state: Utah
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medizinische Universitaetsklinik
city: Linz
country: Austria
facility: Elisabethinen Krankenhaus
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Schwestern
city: Salzburg
country: Austria
facility: Univ. Klinik fur Innere Medizin III LKH
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: AKH Wien
city: Wien
country: Austria
facility: Hanusch Krankenhaus
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Stuivenberg
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende
city: Brussels
country: Belgium
facility: Universite Catholique de Louvain
city: La Louviere
country: Belgium
facility: Centre Hospitalier De Jolimont-Lobbes
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Godinne
city: Amiens
country: France
facility: CHU d'Amiens Hopital Sud
city: Bayonne
country: France
facility: Centre Hospitalier de la Cote Basque
city: Lyon
country: France
facility: CHU de Lyon - Hopital Edouard Herriot
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: CHRU De Montpellier Hopital St. Eloi
city: Mulhouse
country: France
facility: Centre Hospitalier De Mulhouse
city: Paris
country: France
facility: Hopital St Louis Universite Paris 7
city: Perigueux
country: France
facility: Centre Hospitalier de Perigueux
city: Pringy
country: France
facility: Centre Hospitalier d'Annecy
city: St Brieuc
country: France
facility: Centre Hospitalier de Saint-Brieuc Yves Ie Foll
city: Strasbourg
country: France
facility: CHU de Strasbourg - Hopital Civil
city: Strasbourg
country: France
facility: Strasbourg Oncologie Liberale
city: Tours
country: France
facility: CHU de Tours Hopital Bretonneau
city: Berlin
country: Germany
facility: Universitaetsklinikum Charite Berlin, Campus Benjamin Franklin
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl-Gustav-Carus Dresden
city: Duisburg
country: Germany
facility: St. Johannes Hospital
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Hoechst
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heilbronn
country: Germany
facility: SLK Kliniken Heilbronn
city: Leipzig
country: Germany
facility: Klinikum St. Georg
city: Minden
country: Germany
facility: Johannes Wesling Klinikum
city: Muenchen
country: Germany
facility: TU Muenchen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Győr
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Kaposvár
country: Hungary
facility: Kaposi Mor Oktato Korhaz
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti Umberto I
city: Bergamo
country: Italy
facility: AO Ospedali Riuniti di Bergamo
city: Bologna
country: Italy
facility: Universita di Bologna Ist Ematologia Oncologia Medica Seragnoli
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia
city: Campobasso
country: Italy
facility: Universita Cattolica del Sacro Cuore
city: Firenze
country: Italy
facility: AOU Careggi
city: Genova
country: Italy
facility: AOU San Martino IST
city: Lecce
country: Italy
facility: PO Vito Fazzi
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: AORN Antonio Cardarelli
city: Napoli
country: Italy
facility: Uni. Napoli Ospedale Federico lI
city: Novara
country: Italy
facility: AOU Maggiore della Carità di Novara
city: Palermo
country: Italy
facility: AOOR Villa Sofia Cervello di Palermo
city: Pavia
country: Italy
facility: Policlinico San Matteo Di Pavia
city: Torino
country: Italy
facility: AOU San Luigi Gonzaga
city: Gdansk
country: Poland
facility: Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Legnica
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Legnicy
city: Lodz
country: Poland
facility: University of Lodz N. Copernicus Memorial Hospital
city: Warsaw
country: Poland
facility: IHT Instytut Hematologii I Transfuzjologii w Warszawie
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 w Wroclawiu
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ICO Badalona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital De La Santa Creu Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari "La Fe"
city: Luleå
country: Sweden
facility: Sunderby Hospital
city: Lund
country: Sweden
facility: Skåne Universitetssjukhus Univ Hospital Lund
city: Bern
country: Switzerland
facility: Inselspital Bern
city: London
country: United Kingdom
facility: Kings College Hospital and Guys and St Thomas' Hospital
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Hagop M Kantarjian, M.D.
role: STUDY_CHAIR
References:
citation: Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. doi: 10.1002/cncr.33828. Epub 2021 Aug 23.