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

• Complete remission with duration [ Time Frame: Up to 43 months ] [ Designated as safety issue: Yes ]
• Complete remission with incomplete platelet count recovery and duration [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]
• Partial remission with duration [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]
• Hematological improvement with duration [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]
• Stable disease with duration [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]
• Number of units of blood product transfused [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
• Hospitalized days [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]
• 1-year survival [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]

• Complete remission with duration [ Time Frame: Up to 39 months ] [ Designated as safety issue: Yes ]
• Complete remission with incomplete platelet count recovery and duration [ Time Frame: up to 39 months ] [ Designated as safety issue: Yes ]
• Partial remission with duration [ Time Frame: up to 39 months ] [ Designated as safety issue: Yes ]
• Hematological improvement with duration [ Time Frame: up to 39 months ] [ Designated as safety issue: Yes ]
• Stable disease with duration [ Time Frame: up to 39 months ] [ Designated as safety issue: Yes ]
• Number of units of blood product transfused [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]
• Hospitalized days [ Time Frame: up to 39 months ] [ Designated as safety issue: Yes ]
• 1-year survival [ Time Frame: up to 39 months ] [ Designated as safety issue: Yes ]

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.

This is a multicenter, randomized, Phase 3 study 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.

• Drug: Sapacitabine and decitabine
  Sapacitabine administered in alternating cycles with decitabine
• Drug: Decitabine
  Decitabine alone

• Experimental: Arm A
  Sapacitabine and decitabine
  Intervention: Drug: Sapacitabine and decitabine
• Active Comparator: Arm C
  Decitabine
  Intervention: Drug: Decitabine

Inclusion Criteria:

• Newly diagnosed AML based on WHO 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 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 the preceding MDS or MPD
• Known or suspected central nervous system (CNS) involvement by leukemia
• Uncontrolled intercurrent illness
• Known hypersensitivity to decitabine
• Known to be HIV-positive