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

Phase 3

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Sapacitabine; Drug: Decitabine

• Registration Number: NCT01303796
• Lead Sponsor: Cyclacel Pharmaceuticals, Inc.

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.

Study Timeline

• Study First Submitted: 2011-02-21
• Study First Submitted QC: 2011-02-24
• Study First Posted: 2011-02-25
• Study Start: 2011-10-01
• Primary Completion: 2016-12-15
• Study Completion: 2017-07-31
• Results First Submitted: 2021-12-07
• Status Verified: 2022-05
• Results First Submitted QC: 2022-05-26
• Last Update Submitted: 2022-05-26
• Results First Posted: 2022-06-22
• Last Update Posted: 2022-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 482

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sapacitabine-decitabine alternating	Decitabine	Arm A sapacitabine administered in alternating cycles with decitabine
Decitabine	Decitabine	Arm C Decitabine
Sapacitabine-decitabine alternating	Sapacitabine	Arm A sapacitabine administered in alternating cycles with decitabine

Primary Outcome Measures

Name	Time	Method
Overall Survival	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 Outcome Measures

Name	Time	Method
Complete Remission With Incomplete Platelet Count Recovery (CRp)	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
1-year Survival	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.
Partial Remission (PR)	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
Complete Remission (CR)	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
Hematological Improvement	up to 43 months	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
Blood Products Transfused	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.
Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp)	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
Duration of Hematological Improvement (dHI)	up to 43 months	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
Duration of Stable Disease (dSD)	up to 43 months	Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks.
Hospitalized Days	up to 12 months	In-patient days in hospital.
Duration of Partial Remission (dPR)	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
Duration of Complete Remission (dCR)	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
Stable Disease (SD)	up to 43 months	Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks.

Trial Locations

Locations (117)

University of Alabama Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Scripps Cancer Center; 🇺🇸 La Jolla, California, United States

UCLA Ronald Reagan Medical Center; 🇺🇸 Los Angeles, California, United States

Norwalk Hospital; 🇺🇸 Norwalk, Connecticut, United States

Shands Cancer Hospital at University of Florida; 🇺🇸 Gainesville, Florida, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Winship Cancer Institute, Emory University; 🇺🇸 Atlanta, Georgia, United States

Blood and Marrow Transplant Group of Georgia; 🇺🇸 Atlanta, Georgia, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

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