Trial Outcomes & Findings for Rabbit Antithymocyte Globulin Versus Campath-1H for Treating Severe Aplastic Anemia (NCT NCT00065260)

NCT ID: NCT00065260

Last Updated: 2021-07-21

Results Overview

Number of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment at 6 months

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 54 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2021-07-21

Participant Flow

Participant milestones

Measure	r-ATG /Cyclosporine A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Overall Study STARTED	27	27
Overall Study COMPLETED	27	26
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	r-ATG /Cyclosporine A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Overall Study Death	0	1

Baseline Characteristics

Rabbit Antithymocyte Globulin Versus Campath-1H for Treating Severe Aplastic Anemia

Baseline characteristics by cohort

Measure	r-ATG /Cyclosporine n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).	Total n=54 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	14 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	27 participants n=7 Participants	54 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: 1 patient was not evaluable at 6 months in the alemtuzumab arm because of a single early death from infectious complications

Number of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment at 6 months

Outcome measures

Measure	r-ATG /Cyclosporine n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=26 Participants A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Participants no Longer Meeting Criteria for Severe Aplastic Anemia. No Response	18 participants	17 participants
Participants no Longer Meeting Criteria for Severe Aplastic Anemia. Partial Response	9 participants	9 participants
Participants no Longer Meeting Criteria for Severe Aplastic Anemia. Complete Response	0 participants	0 participants

SECONDARY outcome

Timeframe: 6 months

Population: 1 patient was not evaluable at 6 months in the alemtuzumab arm because of a single early death from infectious complications

Number of participants with robust hematologic recovery with reticulocyte or platelet count ≥ 50,000/uL

Outcome measures

Measure	r-ATG /Cyclosporine n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=26 Participants A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Number of Participants With Robust Hematologic Recovery With Reticulocyte or Platelet Count	9 Participants	9 Participants

SECONDARY outcome

Timeframe: 3 year

Population: 1 participants was not evaluable at 6 months in the alemtuzumab arm because of a single early death from infectious complications.

Percentage of cumulative incidence of relapse of disease in participants

Outcome measures

Measure	r-ATG /Cyclosporine n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=26 Participants A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Percentage of Cumulative Incidence of Relapse in Participants	19 percentage of cumulative incidence	9 percentage of cumulative incidence

SECONDARY outcome

Timeframe: 3 years

Population: 1 participant was not evaluable at 6 months in the alemtuzumab arm because of a single early death from infectious complications

Percent of cumulative incidence of clonal evolution in participants to either paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia or acute leukemia.

Outcome measures

Measure	r-ATG /Cyclosporine n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=26 Participants A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Percentage of Cumulative Incidence of Clonal Evolution in Participants	16 Percentage of Cumulative Incidence	5 Percentage of Cumulative Incidence

SECONDARY outcome

Timeframe: 3 months and 6 months

Population: 1 patient was not evaluable at 6 months in the alemtuzumab arm because of a single early death from infectious complications

Percentage of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment

Outcome measures

Measure	r-ATG /Cyclosporine n=27 Participants A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=26 Participants A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Percentage of Participants no Longer Meeting Criteria for Severe Aplastic Anemia. 3 Months	19 percentage of participants Interval 3.0 to 34.0	19 percentage of participants Interval 3.0 to 34.0
Percentage of Participants no Longer Meeting Criteria for Severe Aplastic Anemia. 6 Months	33 percentage of participants Interval 14.0 to 52.0	37 percentage of participants Interval 18.0 to 57.0

Adverse Events

r-ATG /Cyclosporine

Serious events: 7 serious events

Other events: 7 other events

Deaths: 9 deaths

Alemtuzumab (Campath-1H)

Serious events: 12 serious events

Other events: 12 other events

Deaths: 4 deaths

Serious adverse events

Measure	r-ATG /Cyclosporine n=27 participants at risk A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=27 participants at risk A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Immune system disorders infection	25.9% 7/27 • Number of events 7 • 3 years	44.4% 12/27 • Number of events 12 • 3 years

Other adverse events

Measure	r-ATG /Cyclosporine n=27 participants at risk A randomized trial of rabbit anti-thymocyte globulin (r-ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). r-ATG: Rabbit ATG 3.5mg/kg/day for consecutive 5 days CsA: CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.	Alemtuzumab (Campath-1H) n=27 participants at risk A randomized trial of rabbit anti-thymocyte globulin (ATG)/ cyclosporine (CsA) versus Campath-1H in aplastic anemia patients with refractory pancytopenia or suboptimal hematological response after horse ATG treatment. Subjects who receive rabbit ATG/ CsA will be given rabbit ATG 3.5mg/kg/day for 5 days and CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs. Subjects who receive Campath-1H will receive an intravenous infusion for 10 days. Adult subjects will receive 10mg/day (children:0.2mg/kg/day). Campath-1H: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Blood and lymphatic system disorders infection	25.9% 7/27 • Number of events 7 • 3 years	44.4% 12/27 • Number of events 12 • 3 years

Additional Information

Dr. Bhavisha Patel

NIH NHLBI

Phone: 301.402.3477

Email: bhavisha.patel@nih.gov

Results disclosure agreements

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