Trial Outcomes & Findings for Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia (NCT NCT00661726)

NCT ID: NCT00661726

Last Updated: 2014-04-25

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: up to 12 weeks
• Results posted on: 2014-04-25

Participant Flow

Recruitment began in early 2007 at one site, Toronto General Hospital. When recruitment became too challenging, the study was moved to the Thalassemia Clinical Research Network and opened at 2 more sites in 2008. These included Children's Hospital in Philadelphia and Children's Hospital in Oakland. Recruitment closed in May, 2010 with 6 subjects.

To be eligible, patients had to be >=18 years of age and have beta thalassemia intermedia or beta thalassemia-HbE intermedia, no transfusions for 120 days, no hydroxyurea for 120 days, have RBC folate levels above the lower limit of normal, and steady-state anemia (post pt #2, the protocol was amended to define anemia hemoglobin level of <10g/dl).

Participant milestones

Measure	Phase IIA Open Label, Single-arm, Multi-center Pilot Study Participants will receive injected decitabine for 12 weeks.
Overall Study STARTED	6
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Phase IIA Open Label, Single-arm, Multi-center Pilot Study Participants will receive injected decitabine for 12 weeks.
Overall Study Adverse Event	1

Baseline Characteristics

Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia

Baseline characteristics by cohort

Measure	Phase IIA Open Label, Single-arm, Multi-center Pilot Study n=6 Participants Participants will receive injected decitabine for 12 weeks.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	39.2 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants
Patients that had been splenectomized Yes	5 participants n=5 Participants
Patients that had been splenectomized No	1 participants n=5 Participants
Received transfusion in preceding year but > 120 days before protocol therapy Yes	4 participants n=5 Participants
Received transfusion in preceding year but > 120 days before protocol therapy No	2 participants n=5 Participants
Baseline Hemoglobin	7.9 g/dl STANDARD_DEVIATION 1.8 • n=5 Participants
Documented Concomitant Mutation at the alpha-globin locus Yes	1 participants n=5 Participants
Documented Concomitant Mutation at the alpha-globin locus No	5 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Number of Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL	2 participants

PRIMARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Total Hemoglobin (Hb) From Baseline to Peak (the Follow-up Time Point With the Highest Value)	1.16 g/dL Standard Error 0.20

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Absolute Fetal Hemoglobin (HbF) From Baseline to Peak (the Follow-up Time Point With the Highest Value)	0.65 g/dL Standard Error 0.06

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Indirect Bilirubin From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)	-17.36 µmol/L Standard Error 6.95

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Serum Lactate Dehydrogenase (LDH) From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)	-116.60 U/L Standard Error 40.81

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Absolute Reticulocyte Count From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)	-34.00 X (10^9)/L Standard Error 12.50

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Erythropoietin Levels From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)	-43.78 mIU/mL Standard Error 21.60

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Platelet Count From Baseline to Peak (the Follow-up Time Point With the Highest Value)	355.0 X (10^9)/L Standard Error 102.0

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Neutrophil Counts From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)	-3.15 X (10^9)/L Standard Error 1.03

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Deformability was assessed by ektacytometry. Normal RBC have maximal deformability, measurable by osmotic ektacytometry, at isotonicity (290 mosmol). A decrease on the Deformability Index (measured in arbitrary units) corresponds to an impairment in the cell membrane's ability to alter its shape under stress.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Red Blood Cell (RBC) Deformability From Baseline to Peak (the Follow-up Time Point With the Highest Value) Baseline	0.43 Arbitrary Units Standard Error 0.03
Change in Red Blood Cell (RBC) Deformability From Baseline to Peak (the Follow-up Time Point With the Highest Value) Change From Baseline	0.09 Arbitrary Units Standard Error 0.05

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Percentage of Red Blood Cell (RBC) Hb Concentration From Baseline to Peak (the Follow-up Time Point With the Highest Value)	7.06 % of RBC Hb Concentration Standard Error 1.56

SECONDARY outcome

Timeframe: up to 12 weeks

Population: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

Outcome measures

Measure	Decitabine n=5 Participants Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Change in Percentage of Annexin-positive Cells From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)	-1.26 % of Annexin-Positive Cells Standard Error 0.55

Adverse Events

Decitabine

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Decitabine n=5 participants at risk Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Blood and lymphatic system disorders High Platelets Count	60.0% 3/5 • Number of events 3

Other adverse events

Measure	Decitabine n=5 participants at risk Decitabine 0.2 mg/kg was administered subcutaneously daily on the same 2 consecutive days each week for 12 weeks.
Musculoskeletal and connective tissue disorders Fracture	20.0% 1/5 • Number of events 1
Vascular disorders Ocular/ visual- other: Conjunctival Infection	20.0% 1/5 • Number of events 1
General disorders Radiating Pain in Right Shoulder	20.0% 1/5 • Number of events 1
General disorders Pain - joint	20.0% 1/5 • Number of events 1
Cardiac disorders Palpitation	20.0% 1/5 • Number of events 1

Additional Information

Nancy Gee, TCRN Network Manager

NERI

Phone: 617-972-3295

Email: ngee@neriscience.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place