A Study of Oral Sapacitabine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

— SEAMLESS  

Official title:

A Phase III Randomized Study of Oral Sapacitabine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01303796
• Other study ID #: CYC682-12
• Status: Completed
• Phase: Phase 3
• Start date: October 1, 2011
• Est. completion date: July 31, 2017

Study information

• Verified date: May 2022
• Source: Cyclacel Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 482
• Est. completion date: July 31, 2017
• Est. primary completion date: December 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Sapacitabine
Oral sapacitabine capsules
• Decitabine
Decitabine intravenous

Locations

Country	Name	City	State
Austria	Medizinische Universitaetsklinik	Innsbruck
Austria	Elisabethinen Krankenhaus	Linz
Austria	Krankenhaus der Barmherzigen Schwestern	Linz
Austria	Univ. Klinik fur Innere Medizin III LKH	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Austria	AKH Wien	Wien
Austria	Hanusch Krankenhaus	Wien
Belgium	Ziekenhuis Netwerk Antwerpen Stuivenberg	Antwerpen
Belgium	AZ Sint-Jan Brugge-Oostende	Brugge
Belgium	Universite Catholique de Louvain	Brussels
Belgium	Centre Hospitalier De Jolimont-Lobbes	La Louviere
Belgium	Cliniques Universitaires UCL de Mont-Godinne	Yvoir
France	CHU d'Amiens Hopital Sud	Amiens
France	Centre Hospitalier de la Cote Basque	Bayonne
France	CHU de Lyon - Hopital Edouard Herriot	Lyon
France	Institut Paoli Calmettes	Marseille
France	CHRU De Montpellier Hopital St. Eloi	Montpellier
France	Centre Hospitalier De Mulhouse	Mulhouse
France	Hopital St Louis Universite Paris 7	Paris
France	Centre Hospitalier de Perigueux	Perigueux
France	Centre Hospitalier d'Annecy	Pringy
France	Centre Hospitalier de Saint-Brieuc Yves Ie Foll	St Brieuc
France	CHU de Strasbourg - Hopital Civil	Strasbourg
France	Strasbourg Oncologie Liberale	Strasbourg
France	CHU de Tours Hopital Bretonneau	Tours
Germany	Universitaetsklinikum Charite Berlin, Campus Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Carl-Gustav-Carus Dresden	Dresden
Germany	St. Johannes Hospital	Duisburg
Germany	Klinikum Frankfurt Hoechst	Frankfurt
Germany	Asklepios Klinik Altona	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	SLK Kliniken Heilbronn	Heilbronn
Germany	Klinikum St. Georg	Leipzig
Germany	Johannes Wesling Klinikum	Minden
Germany	TU Muenchen	Muenchen
Germany	Universitaetsklinikum Muenster	Muenster
Hungary	University of Debrecen	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Kaposi Mor Oktato Korhaz	Kaposvár
Italy	AOU Ospedali Riuniti Umberto I	Ancona
Italy	AO Ospedali Riuniti di Bergamo	Bergamo
Italy	Universita di Bologna Ist Ematologia Oncologia Medica Seragnoli	Bologna
Italy	AO Spedali Civili di Brescia	Brescia
Italy	Universita Cattolica del Sacro Cuore	Campobasso
Italy	AOU Careggi	Firenze
Italy	AOU San Martino IST	Genova
Italy	PO Vito Fazzi	Lecce
Italy	Ospedale San Raffaele	Milano
Italy	AORN Antonio Cardarelli	Napoli
Italy	Uni. Napoli Ospedale Federico lI	Napoli
Italy	AOU Maggiore della Carità di Novara	Novara
Italy	AOOR Villa Sofia Cervello di Palermo	Palermo
Italy	Policlinico San Matteo Di Pavia	Pavia
Italy	AOU San Luigi Gonzaga	Torino
Poland	Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku	Gdansk
Poland	Wojewodzki Szpital Specjalistyczny	Legnica
Poland	Wojewódzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	University of Lodz N. Copernicus Memorial Hospital	Lodz
Poland	IHT Instytut Hematologii I Transfuzjologii w Warszawie	Warsaw
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Wroclawiu	Wroclaw
Spain	Hospital Universitari Germans Trias i Pujol ICO Badalona	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital De La Santa Creu Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Canarias	La Laguna
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Hospital Universitari Son Espases	Palma de Mallorca
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Clinico Universitario	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari "La Fe"	Valencia
Sweden	Sunderby Hospital	Luleå
Sweden	Skåne Universitetssjukhus Univ Hospital Lund	Lund
Switzerland	Inselspital Bern	Bern
United Kingdom	Kings College Hospital and Guys and St Thomas' Hospital	London
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	University of Maryland Greenbaum Cancer Center	Baltimore	Maryland
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Shands Cancer Hospital at University of Florida	Gainesville	Florida
United States	Saint Francis Hospital	Greenville	South Carolina
United States	John Theurer Cancer Center at the Hackensack University Medical Center	Hackensack	New Jersey
United States	Westchester Hematology Oncology Group, PC	Hawthorne	New York
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	St. Francis Medical Group Oncology and Hematology Specialists	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Scripps Cancer Center	La Jolla	California
United States	Dartmouth - Hitchcock Medical Center	Lebanon	New Hampshire
United States	UCLA Ronald Reagan Medical Center	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Beth Israel Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Norwalk Hospital	Norwalk	Connecticut
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	St. Louis University Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute at the University of Utah	Salt Lake City	Utah
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cyclacel Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  France,  Germany,  Hungary,  Italy,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	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.	up to 43 months
Secondary	Complete Remission (CR)	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	up to 43 months
Secondary	Complete Remission With Incomplete Platelet Count Recovery (CRp)	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 response	up to 43 months
Secondary	Partial Remission (PR)	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 response	up to 43 months
Secondary	Hematological Improvement	HI with duration (HI); 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; 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; 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 response	up to 43 months
Secondary	Stable Disease (SD)	Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for > 16 weeks.	up to 43 months
Secondary	Blood Products Transfused	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.	up to 43 months
Secondary	Hospitalized Days	In-patient days in hospital.	up to 12 months
Secondary	1-year Survival	One-year survival is the percentage of patients who are alive at 1-year measured from the date of randomization.	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).
Secondary	Duration of Complete Remission (dCR)	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	up to 43 months
Secondary	Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp)	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 response	up to 43 months
Secondary	Duration of Partial Remission (dPR)	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 response	up to 43 months
Secondary	Duration of Hematological Improvement (dHI)	Duration of HI; 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; 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; 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 response	up to 43 months
Secondary	Duration of Stable Disease (dSD)	Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for > 16 weeks.	up to 43 months

External Links

•   Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS)