Efficacy Study of Oral Sapacitabine to Treat Acute Myeloi... | NCT00590187

NCT00590187

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
A sapacitabine	Experimental	200 mg b.i.d. x 7 days every 3-4 weeks	Drug: Sapacitabine, Arm A
B sapacitabine	Experimental	300 mg b.i.d. x 7 days every 3 - 4 weeks	Drug: Sapacitabine, Arm B
C sapacitabine	Experimental	400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks	Drug: Sapacitabine, Arm C
D sapacitabine	Experimental	200 mg b.i.d. x 7 consecutive days every 4 weeks	Drug: Sapacitabine, Arm D
E sapacitabine	Experimental	300 mg q.d. x 7 consecutive days every 4 weeks	Drug: sapacitabine, Arm E
F sapacitabine	Experimental	300 mg b.i.d. x 3 consecutive days per week for 2 weeks every 4 weeks

Name	Type	Description	Arm Group Labels	Other Names
Sapacitabine, Arm A	Drug	200 mg b.i.d. x 7 days every 3-4 weeks	A sapacitabine

Measure	Description	Time Frame
Survival	Percentage of patients alive for one year measured from the date of randomization	up to 12 months from date of randomization

Measure	Description	Time Frame
CR and CRp	Complete remission and complete remission without blood count recovery, transfusion requirements, hospitalized days and safety	From date of randomization until study withdrawal or death assessed up to 6 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

A histologically or pathologically confirmed diagnosis of AML based on WHO classification which is previously untreated by systemic therapy or is in first relapse after achieving a complete remission to initial induction, consolidation and/or maintenance therapy or MDS with IPSS scores of intermediate -2 or higher risk risk which has been previously treated with hypomethylating agents
Age 70 years or older for AML and 60 years or older for MDS
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Adequate renal function defined as serum creatinine equal to or less than 1.5 x upper limit of normal (ULN)
Adequate liver function defined as total bilirubin or direct bilirubin equal to or less than 1.5 x ULN; alanine aminotransferase (ALT or SGPT) equal to or less than 2.5 x ULN (5 x ULN if tumor has affected the liver)
Life expectancy reasonably adequate for evaluating the treatment effect
Patient must be able to swallow capsules
Patients must be at least 2 weeks from prior systemic therapy, radiation therapy, major surgery, or other investigational therapy, and have recovered from clinically significant toxicities of these prior treatments
All men and women of reproductive potential must agree to practice effective contraception for 4 weeks prior to study entry, during the entire study period and for one month after the study unless documentation of infertility exists
Ability to understand and willingness to sign the informed consent form

Exclusion Criteria:

AML is of the sub-type of acute promyelocytic leukemia
Having received more than one induction systemic therapy for AML or having received a standard dose or high dose ara-C containing regimen for MDS
Patients with known central nervous system (CNS) involvement by leukemia
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active cancer(s) other than AML, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients receiving intravenous antibiotics for infections that are under control may be included in this study
Known to be HIV-positive

Name	Affiliation	Role
Hagop M Kantarjian, MD	M.D. Anderson Cancer Center	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
UCLA Division of Hematology-Oncology

PubMed Identifier	Type	Citation	Retractions
23075701	Result	Kantarjian H, Faderl S, Garcia-Manero G, Luger S, Venugopal P, Maness L, Wetzler M, Coutre S, Stock W, Claxton D, Goldberg SL, Arellano M, Strickland SA, Seiter K, Schiller G, Jabbour E, Chiao J, Plunkett W. Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study. Lancet Oncol. 2012 Nov;13(11):1096-104. doi: 10.1016/S1470-2045(12)70436-9. Epub 2012 Oct 15.

Label	URL
Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	A Sapacitabine	200 mg b.i.d. x 7 days every 3-4 weeks Sapacitabine, Arm A: 200 mg b.i.d. x 7 days every 3-4 weeks
FG001	B Sapacitabine	300 mg b.i.d. x 7 days every 3 - 4 weeks Sapacitabine, Arm B: 300 mg b.i.d. x 7 days every 3 - 4 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 4, 2010

ID	Title	Description
BG000	A Sapacitabine	Sapacitabine, Arm A: 200 mg b.i.d. x 7 days every 3-4 weeks
BG001	B Sapacitabine	Sapacitabine, Arm B: 300 mg b.i.d. x 7 days every 3 - 4 weeks
BG002	C Sapacitabine	Sapacitabine, Arm C: 400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00040 BG00120 BG00245 BG003105

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Survival

Percentage of patients alive for one year measured from the date of randomization

Arms D through I were terminated prematurely because of financial restrictions. Accordingly the company made the determination of the dosing schedule which was used in the subsequent Phase 3 study based on the results of Arms A through C.

Posted

Number

95% Confidence Interval

percentage of patients alive for one yea

up to 12 months from date of randomization

ID	Title	Description
OG000	A Sapacitabine	200 mg b.i.d. x 7 days every 3-4 weeks Sapacitabine, Arm A: 200 mg b.i.d. x 7 days every 3-4 weeks
OG001	B Sapacitabine	300 mg b.i.d. x 7 days every 3 - 4 weeks Sapacitabine, Arm B: 300 mg b.i.d. x 7 days every 3 - 4 weeks
OG002	C Sapacitabine	400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks Sapacitabine, Arm C: 400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks

Units	Counts
Participants	OG00020 OG00120 OG00220

Title

Denominators

Categories

Title	Measurements
	OG00035(16 to 59) OG00110(2 to 33) OG00230(13 to 54)

Secondary

CR and CRp

Complete remission and complete remission without blood count recovery, transfusion requirements, hospitalized days and safety

Posted

Count of Participants

Participants

From date of randomization until study withdrawal or death assessed up to 6 months

ID	Title	Description
OG000	A Sapacitabine	200 mg b.i.d. x 7 days every 3-4 weeks Sapacitabine, Arm A: 200 mg b.i.d. x 7 days every 3-4 weeks
OG001	B Sapacitabine	300 mg b.i.d. x 7 days every 3 - 4 weeks Sapacitabine, Arm B: 300 mg b.i.d. x 7 days every 3 - 4 weeks
OG002	C Sapacitabine	400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks Sapacitabine, Arm C: 400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks

Units

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0008 events8 affected40 at risk EG00112 events12 affected20 at risk EG00215 events15 affected45 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00016 events16 affected40 at risk EG0019 events9 affected20 at risk EG00222 events22 affected45 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00014 events14 affected40 at risk EG00110 events10 affected20 at risk EG00211 events11 affected45 at risk
Throbocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00024 events24 affected40 at risk EG00112 events12 affected20 at risk EG00222 events22 affected45 at risk
Atrial fibrilation	Cardiac disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0012 events2 affected20 at risk EG0024 events4 affected45 at risk
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0010 events0 affected20 at risk EG0022 events2 affected45 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0011 events1 affected20 at risk EG0020 events0 affected45 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0012 events2 affected20 at risk EG0023 events3 affected45 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0022 events2 affected45 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected40 at risk EG0010 events0 affected20 at risk EG0021 events1 affected45 at risk
Fatigue	General disorders	Systematic Assessment	EG0003 events3 affected40 at risk EG0011 events1 affected20 at risk EG0024 events4 affected45 at risk
Peripheral Oedema	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0022 events2 affected45 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0013 events3 affected20 at risk EG0020 events0 affected45 at risk
Fever	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0020 events0 affected45 at risk
Bacteraemia	Infections and infestations	Systematic Assessment	EG0005 events5 affected40 at risk EG0012 events2 affected20 at risk EG0025 events5 affected45 at risk
Cellulitis	General disorders	Systematic Assessment	EG0003 events3 affected40 at risk EG0013 events3 affected20 at risk EG0025 events5 affected45 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0009 events9 affected40 at risk EG0016 events6 affected20 at risk EG00213 events13 affected45 at risk
Sepsis	General disorders	Systematic Assessment	EG0009 events9 affected40 at risk EG0013 events3 affected20 at risk EG0022 events2 affected45 at risk
Anorexia	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0020 events0 affected45 at risk
Weight decreased	General disorders	Systematic Assessment	EG0000 events0 affected40 at risk EG0010 events0 affected20 at risk EG0021 events1 affected45 at risk
Hypokalemia	Renal and urinary disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0011 events1 affected20 at risk EG0023 events3 affected45 at risk
Arthralgia	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0021 events1 affected45 at risk
Back pain	General disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0010 events0 affected20 at risk EG0020 events0 affected45 at risk
Musculoskeletal chest pain	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0022 events2 affected45 at risk
Headache	General disorders	Systematic Assessment	EG0000 events0 affected40 at risk EG0010 events0 affected20 at risk EG0023 events3 affected45 at risk
Insomnia	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0020 events0 affected45 at risk
Dyspnoea	General disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0010 events0 affected20 at risk EG0022 events2 affected45 at risk
Epistaxis	General disorders	Systematic Assessment	EG0000 events0 affected40 at risk EG0011 events1 affected20 at risk EG0020 events0 affected45 at risk
Ecchymosis	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0011 events1 affected20 at risk EG0021 events1 affected45 at risk
Petechiae	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0020 events0 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0011 events1 affected20 at risk EG0021 events1 affected45 at risk
Hypotension	General disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0010 events0 affected20 at risk EG0024 events4 affected45 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0010 events0 affected20 at risk EG0024 events4 affected45 at risk
Atrial fibrilation	Cardiac disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0012 events2 affected20 at risk EG0022 events2 affected45 at risk
Abdominal pain	General disorders	Systematic Assessment	EG0006 events6 affected40 at risk EG0013 events3 affected20 at risk EG0021 events1 affected45 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG00010 events10 affected40 at risk EG0018 events8 affected20 at risk EG00211 events11 affected45 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00023 events23 affected40 at risk EG00111 events11 affected20 at risk EG00217 events17 affected45 at risk
Nausea	General disorders	Systematic Assessment	EG00016 events16 affected40 at risk EG0016 events6 affected20 at risk EG00223 events23 affected45 at risk
Stomatitis	General disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0012 events2 affected20 at risk EG0027 events7 affected45 at risk
Vomiting	General disorders	Systematic Assessment	EG00012 events12 affected40 at risk EG0015 events5 affected20 at risk EG00211 events11 affected45 at risk
Fatigue	General disorders	Systematic Assessment	EG00019 events19 affected40 at risk EG00110 events10 affected20 at risk EG00213 events13 affected45 at risk
Peripheral Oedema	General disorders	Systematic Assessment	EG0005 events5 affected40 at risk EG0018 events8 affected20 at risk EG00215 events15 affected45 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0012 events2 affected20 at risk EG0020 events0 affected45 at risk
Fever	General disorders	Systematic Assessment	EG0006 events6 affected40 at risk EG0011 events1 affected20 at risk EG0029 events9 affected45 at risk
Bacteraemia	General disorders	Systematic Assessment	EG0002 events2 affected40 at risk EG0011 events1 affected20 at risk EG0020 events0 affected45 at risk
Cellulitis	General disorders	Systematic Assessment	EG0003 events3 affected40 at risk EG0010 events0 affected20 at risk EG0023 events3 affected45 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0011 events1 affected20 at risk EG0021 events1 affected45 at risk
Anorexia	General disorders	Systematic Assessment	EG0009 events9 affected40 at risk EG0015 events5 affected20 at risk EG0028 events8 affected45 at risk
Weight decrease	General disorders	Systematic Assessment	EG0003 events3 affected40 at risk EG0014 events4 affected20 at risk EG0023 events3 affected45 at risk
Hypokalemia	Renal and urinary disorders	Systematic Assessment	EG0003 events3 affected40 at risk EG0010 events0 affected20 at risk EG0024 events4 affected45 at risk
Arthralgia	General disorders	Systematic Assessment	EG0007 events7 affected40 at risk EG0010 events0 affected20 at risk EG0025 events5 affected45 at risk
Back Pain	General disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0011 events1 affected20 at risk EG0026 events6 affected45 at risk
Musculoskeletal chest pain	General disorders	Systematic Assessment	EG0001 events1 affected40 at risk EG0010 events0 affected20 at risk EG0026 events6 affected45 at risk
Pain in extremity	General disorders	Systematic Assessment	EG0007 events7 affected40 at risk EG0011 events1 affected20 at risk EG0028 events8 affected45 at risk
Dizziness	General disorders	Systematic Assessment	EG0007 events7 affected40 at risk EG0013 events3 affected20 at risk EG00210 events10 affected45 at risk
Headache	General disorders	Systematic Assessment	EG0007 events7 affected40 at risk EG0010 events0 affected20 at risk EG0026 events6 affected45 at risk
Insomnia	General disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0011 events1 affected20 at risk EG0027 events7 affected45 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0009 events9 affected40 at risk EG0013 events3 affected20 at risk EG0026 events6 affected45 at risk
Dyspnoea	General disorders	Systematic Assessment	EG00015 events15 affected40 at risk EG0012 events2 affected20 at risk EG00210 events10 affected45 at risk
Epistaxis	General disorders	Systematic Assessment	EG0006 events6 affected40 at risk EG0013 events3 affected20 at risk EG0025 events5 affected45 at risk
Ecchymosis	General disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0013 events3 affected20 at risk EG0021 events1 affected45 at risk
Petechiae	General disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0013 events3 affected20 at risk EG0027 events7 affected45 at risk
Alopecia	General disorders	Systematic Assessment	EG0007 events7 affected40 at risk EG0012 events2 affected20 at risk EG00210 events10 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0005 events5 affected40 at risk EG0011 events1 affected20 at risk EG0027 events7 affected45 at risk
Hypotension	General disorders	Systematic Assessment	EG0004 events4 affected40 at risk EG0010 events0 affected20 at risk EG0023 events3 affected45 at risk

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	A Sapacitabine	200 mg b.i.d. x 7 days every 3-4 weeks Sapacitabine, Arm A: 200 mg b.i.d. x 7 days every 3-4 weeks	8	40	40	40	40	40
EG001	B Sapacitabine	300 mg b.i.d. x 7 days every 3 - 4 weeks Sapacitabine, Arm B: 300 mg b.i.d. x 7 days every 3 - 4 weeks	6	20	20	20	20	20
EG002	C Sapacitabine	400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks Sapacitabine, Arm C: 400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks	4	45	45	45	45	45