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Acute Myeloid LeukemiaPhase 3SEAMLESSNCT01303796

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

A Phase 3 study testing Sapacitabine and Decitabine in people with Acute Myeloid Leukemia, run by Cyclacel Pharmaceuticals, Inc. at 118 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 70 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Sapacitabine and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
482 participants
Where
118 sitesin 12 countries
Study dates
1 Oct 2011to 31 Jul 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

118 sites in 12 countries.

118 sites in 12 countries

United States39 sites

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

  • Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

  • University of Maryland Greenbaum Cancer Center

    Baltimore, Maryland, 21201

  • University of Alabama Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Shands Cancer Hospital at University of Florida

    Gainesville, Florida, 32608

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • John Theurer Cancer Center at the Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Westchester Hematology Oncology Group, PC

    Hawthorne, New York, 10532

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • MD Anderson Cancer Center

    Houston, Texas, 77030-3387

  • St. Francis Medical Group Oncology and Hematology Specialists

    Indianapolis, Indiana, 46237

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Saint Luke's Cancer Institute

    Kansas City, Missouri, 64111

  • Scripps Cancer Center

    La Jolla, California, 92037

  • Dartmouth - Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • UCLA Ronald Reagan Medical Center

    Los Angeles, California, 90095

  • Joe Arrington Cancer Research and Treatment Center

    Lubbock, Texas, 79410

  • The Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Beth Israel Medical Center

    New York, New York, 10003

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Norwalk Hospital

    Norwalk, Connecticut, 06850

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute at the University of Utah

    Salt Lake City, Utah, 84112

  • St. Louis University Cancer Center

    St Louis, Missouri, 63110

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Italy15 sites

  • AOU Ospedali Riuniti Umberto I

    Ancona

  • AO Ospedali Riuniti di Bergamo

    Bergamo

  • Universita di Bologna Ist Ematologia Oncologia Medica Seragnoli

    Bologna

  • AO Spedali Civili di Brescia

    Brescia

  • Universita Cattolica del Sacro Cuore

    Campobasso

  • AOU Careggi

    Florence

  • AOU San Martino IST

    Genova

  • PO Vito Fazzi

    Lecce

  • Ospedale San Raffaele

    Milan

  • AORN Antonio Cardarelli

    Naples

  • Uni. Napoli Ospedale Federico lI

    Naples

  • AOU Maggiore della Carità di Novara

    Novara

  • AOOR Villa Sofia Cervello di Palermo

    Palermo

  • Policlinico San Matteo Di Pavia

    Pavia

  • AOU San Luigi Gonzaga

    Torino

Other trials in Italy

Spain15 sites

  • Hospital Universitari Germans Trias i Pujol ICO Badalona

    Badalona

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital De La Santa Creu Sant Pau

    Barcelona

  • Hospital Universitario Vall d'Hebron

    Barcelona

  • Hospital Universitario Ramon y Cajal

    Madrid

  • MD Anderson Cancer Center

    Madrid

  • Hospital Son Llatzer

    Palma de Mallorca

  • Hospital Universitari Son Espases

    Palma de Mallorca

  • Clínica Universidad de Navarra

    Pamplona

  • Complejo Hospitalario de Navarra

    Pamplona

  • Hospital Clinico Universitario de Salamanca

    Salamanca

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna

  • Hospital Clinico Universitario

    Santiago de Compostela

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitari "La Fe"

    Valencia

Other trials in Spain

France13 sites

  • CHU d'Amiens Hopital Sud

    Amiens

  • Centre Hospitalier de la Cote Basque

    Bayonne

  • CHU de Lyon - Hopital Edouard Herriot

    Lyon

  • Institut Paoli Calmettes

    Marseille

  • CHRU De Montpellier Hopital St. Eloi

    Montpellier

  • Centre Hospitalier De Mulhouse

    Mulhouse

  • Hopital St Louis Universite Paris 7

    Paris

  • Centre Hospitalier de Perigueux

    Périgueux

  • Centre Hospitalier d'Annecy

    Pringy

  • Centre Hospitalier de Saint-Brieuc Yves Ie Foll

    Saint-Brieuc

  • CHU de Strasbourg - Hopital Civil

    Strasbourg

  • Strasbourg Oncologie Liberale

    Strasbourg

  • CHU de Tours Hopital Bretonneau

    Tours

Other trials in France

Germany11 sites

  • Universitaetsklinikum Charite Berlin, Campus Benjamin Franklin

    Berlin

  • Universitaetsklinikum Carl-Gustav-Carus Dresden

    Dresden

  • St. Johannes Hospital

    Duisburg

  • Klinikum Frankfurt Hoechst

    Frankfurt

  • Asklepios Klinik Altona

    Hamburg

  • Medizinische Hochschule Hannover

    Hanover

  • SLK Kliniken Heilbronn

    Heilbronn

  • Klinikum St. Georg

    Leipzig

  • Johannes Wesling Klinikum

    Minden

  • TU Muenchen

    München

  • Universitaetsklinikum Muenster

    Münster

Other trials in Germany

Austria7 sites

  • Medizinische Universitaetsklinik

    Innsbruck

  • Elisabethinen Krankenhaus

    Linz

  • Krankenhaus der Barmherzigen Schwestern

    Linz

  • Univ. Klinik fur Innere Medizin III LKH

    Salzburg

  • AKH Wien

    Vienna

  • Hanusch Krankenhaus

    Vienna

  • Klinikum Wels-Grieskirchen GmbH

    Wels

Other trials in Austria

Poland6 sites

  • Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku

    Gdansk

  • Wojewodzki Szpital Specjalistyczny

    Legnica

  • Wojewódzki Szpital Specjalistyczny w Legnicy

    Legnica

  • University of Lodz N. Copernicus Memorial Hospital

    Lodz

  • IHT Instytut Hematologii I Transfuzjologii w Warszawie

    Warsaw

  • Samodzielny Publiczny Szpital Kliniczny Nr 1 w Wroclawiu

    Wroclaw

Other trials in Poland

Belgium5 sites

  • Ziekenhuis Netwerk Antwerpen Stuivenberg

    Antwerp

  • AZ Sint-Jan Brugge-Oostende

    Bruges

  • Universite Catholique de Louvain

    Brussels

  • Centre Hospitalier De Jolimont-Lobbes

    La Louvière

  • Cliniques Universitaires UCL de Mont-Godinne

    Yvoir

Other trials in Belgium

Hungary3 sites

  • University of Debrecen

    Debrecen

  • Petz Aladar Megyei Oktato Korhaz

    Győr

  • Kaposi Mor Oktato Korhaz

    Kaposvár

Other trials in Hungary

Sweden2 sites

  • Sunderby Hospital

    Luleå

  • Skåne Universitetssjukhus Univ Hospital Lund

    Lund

Other trials in Sweden

Switzerland1 site

  • Inselspital Bern

    Bern

Other trials in Switzerland

United Kingdom1 site

  • Kings College Hospital and Guys and St Thomas' Hospital

    London

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Being tested
Sapacitabine, Decitabine
Keywords
AML
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SapacitabineDrug

    Also called CYC682

    Oral sapacitabine capsules

  • DecitabineDrug

    Also called Decitabine intravenous

    Decitabine intravenous

Study groups in NCT01303796
Study groupRoleWhat they receive
Sapacitabine-decitabine alternatingExperimentalArm A sapacitabine administered in alternating cycles with decitabine
Receives: Drug: Sapacitabine; Drug: Decitabine
DecitabineActive comparatorArm C Decitabine
Receives: Drug: Decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to 43 months

Secondary outcomes (13)

  1. 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

    Measured: up to 43 months

  2. 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

    Measured: up to 43 months

  3. 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

    Measured: up to 43 months

  4. Hematological Improvement

    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 response

    Measured: up to 43 months

  5. Stable Disease (SD)

    Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for > 16 weeks.

    Measured: up to 43 months

  6. 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.

    Measured: up to 43 months

  7. Hospitalized Days

    In-patient days in hospital.

    Measured: up to 12 months

  8. 1-year Survival

    One-year survival is the percentage of patients who are alive at 1-year measured from the date of randomization.

    Measured: 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).

  9. 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

    Measured: up to 43 months

  10. 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

    Measured: up to 43 months

  11. 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

    Measured: up to 43 months

  12. Duration of Hematological Improvement (dHI)

    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 response

    Measured: up to 43 months

  13. Duration of Stable Disease (dSD)

    Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for > 16 weeks.

    Measured: up to 43 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2011 (estimated)
  2. Study start1 Oct 2011
  3. Primary completion15 Dec 2016
  4. Study completion31 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
482 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01303796
Sponsor's protocol ID
CYC682-12
Acronym
SEAMLESS
Status last verified
May 2022
First submitted
21 Feb 2011
Last updated
22 Jun 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34424530

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sapacitabine and Decitabine in people with Acute Myeloid Leukemia, run by Cyclacel Pharmaceuticals, Inc. at 118 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 118 sites in United States, Italy, Spain, France, Germany and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: up to 43 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01303796, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2022.

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