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Completed

NCT Number: NCT01303796

A 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.

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Key information

Conditions

Acute Myeloid Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

70 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Medizinische Universitaetsklinik, Innsbruck, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sapacitabine

Drug

Oral sapacitabine capsules

Other names: CYC682

decitabine

Drug

Decitabine intravenous

Other names: Decitabine intravenous

Primary outcomes

  1. Overall Survival

    Time frame: 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 outcomes

  1. Complete Remission (CR)

    Time frame: 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 response

  2. Complete Remission With Incomplete Platelet Count Recovery (CRp)

    Time frame: 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 response

  3. Partial Remission (PR)

    Time frame: 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 response

  4. Hematological Improvement

    Time frame: up to 43 months

    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

  5. Stable Disease (SD)

    Time frame: up to 43 months

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

  6. Blood Products Transfused

    Time frame: 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.

  7. Hospitalized Days

    Time frame: up to 12 months

    In-patient days in hospital.

  8. 1-year Survival

    Time frame: 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.

  9. Duration of Complete Remission (dCR)

    Time frame: 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

  10. Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp)

    Time frame: 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 response

  11. Duration of Partial Remission (dPR)

    Time frame: 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 response

  12. Duration of Hematological Improvement (dHI)

    Time frame: up to 43 months

    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

  13. Duration of Stable Disease (dSD)

    Time frame: up to 43 months

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

Sponsors and collaborators

Lead sponsor

Cyclacel Pharmaceuticals, Inc.

Industry

Registry information

Official study title

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

Acronym: SEAMLESS

Important dates

Study start
2011
Primary completion
2016
Study completion
2017
First posted
Feb 25, 2011
Registry last updated
Jun 22, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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