Trial Outcomes & Findings for Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia (NCT NCT00005937)

NCT ID: NCT00005937

Last Updated: 2014-10-23

Results Overview

Red blood cell transfusion independence was documented as time from last transfusion of red cells to last day of transfusion free follow-up. Independence or response to the intervention was assessed by weekly blood counts. Transfusion independence was defined as no transfusion requirement for a 3 month period. Complete hematologic response is defined as the normalization of affected cells lines and less than 5% marrow blasts present. Partial hematologic response is defined as greater than 50% improvement from baseline to normal levels of all cell counts and greater than 50% decrease in marrow blasts.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2014-10-23

Participant Flow

Participant milestones

Measure	MDS Subjects Treated With ATG & CsA Myelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.
Overall Study STARTED	42
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure

MDS Subjects Treated With ATG & CsA Myelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.

Overall Study Lack of Efficacy

5

Baseline Characteristics

Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia

Baseline characteristics by cohort

Measure	MDS Subjects Treated With ATG and CsA n=42 Participants Myelodysplastic syndromes (MDS) subjects will be treated with Antithymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration, the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants
Age, Continuous	54 years STANDARD_DEVIATION 14 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Region of Enrollment United States	42 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Red blood cell transfusion independence was documented as time from last transfusion of red cells to last day of transfusion free follow-up. Independence or response to the intervention was assessed by weekly blood counts. Transfusion independence was defined as no transfusion requirement for a 3 month period. Complete hematologic response is defined as the normalization of affected cells lines and less than 5% marrow blasts present. Partial hematologic response is defined as greater than 50% improvement from baseline to normal levels of all cell counts and greater than 50% decrease in marrow blasts.

Outcome measures

Measure	MDS Subjects Treated With ATG and CsA n=37 Participants Myelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.
Red Blood Cell Transfusion Independence Complete hematologic response	6 participants
Red Blood Cell Transfusion Independence Partial hematologic response	10 participants
Red Blood Cell Transfusion Independence No hematologic response	21 participants

Adverse Events

MDS Subjects Treated With ATG and CsA

Serious events: 11 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	MDS Subjects Treated With ATG and CsA n=42 participants at risk Myelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.
Infections and infestations Death	16.7% 7/42 • Number of events 7
General disorders Hospitalization pulmonary related	4.8% 2/42 • Number of events 2
Cardiac disorders Hospitalization cardiac related	2.4% 1/42 • Number of events 1
Blood and lymphatic system disorders Hospitalization	2.4% 1/42 • Number of events 1

Other adverse events

Measure

MDS Subjects Treated With ATG and CsA n=42 participants at risk Myelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.

Blood and lymphatic system disorders Toxicity with disease progression

4.8% 2/42 • Number of events 2

Additional Information

Neal S. Young MD

NIH National Heart, Lung and Blood Institute

Phone: 301-402-1806

Email: youngns@nhlbi.nih.gov

Results disclosure agreements

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