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

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00065260
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 147
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Severe aplastic anemia, characterized by pancytopenia and a hypocellular bone marrow, is effectively treated by immunosuppressive therapy, usually a combination of antithymocyte globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of patients will not show blood count improvement after ATG/CsA. General experience and small pilot studies have suggested that such patients may benefit from further immunosuppression. Furthermore, analysis of our own clinical data suggest that patients with poor blood count responses to a single course of ATG, even when transfusion-independence is achieved, have a markedly worse prognosis than patients with robust hematologic improvement. The management of such cases is uncertain.

This study will enroll patients who are either refractory to h-ATG (continued severe pancytopenia) or who have only modest improvement in blood counts (weak hematologic responders) to receive a further immunosuppressive therapy, delivered either as rabbit ATG (Thymoglobulin, r-ATG) or a humanized monoclonal antibody to T-cells, alemtuzumab (Campath-1H ). Primary endpoint will be response rate at 3 months defined as no longer meeting criteria for severe aplastic anemia. Relapse, robustness of hematopoietic recovery at 3 months, survival and clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia and acute leukemia will be the secondary endpoints.

Condition or Disease	Intervention/Treatment	Phase
Aplastic Anemia	Drug: Campath-1H; Drug: r-ATG; Drug: CsA	Phase 2

Detailed Description

Severe aplastic anemia, characterized by pancytopenia and a hypocellular bone marrow, is effectively treated by immunosuppressive therapy, usually a combination of antithymocyte globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of patients will not show blood count improvement after ATG/CsA. General experience and small pilot studies have suggested that such patients may benefit from further immunosuppression. Furthermore, analysis of our own clinical data suggest that patients with poor blood count responses to a single course of ATG, even when transfusion-independence is achieved, have a markedly worse prognosis than patients with robust hematologic improvement. The management of such cases is uncertain.

This study will enroll patients who are either refractory to h-ATG (continued severe pancytopenia) or who have only modest improvement in blood counts (weak hematologic responders) to receive further immunosuppressive therapy, delivered either as rabbit ATG (Thymoglobulin , r-ATG) or a humanized monoclonal antibody to T-cells, alemtuzumab (Campath-1H ). Primary endpoint will be response rate at 6 months defined as no longer meeting criteria for severe aplastic anemia. Relapse, robustness of hematopoietic recovery at 6 months, survival and clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia and acute leukemia will be the secondary endpoints.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial of Immunosuppression in Aplastic Anemia Patients With Refractory Pancytopenia or Suboptimal Hematologic Response After h-ATG/CsA Treatment
• Actual Study Start Date: Nov 6, 2003
• Actual Primary Completion Date: Dec 29, 2010
• Actual Study Completion Date: Feb 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: r-ATG; Rabbit ATG 3.5mg/kg/day for consecutive 5 days; Other Names: Rabbit Anti-Thymoglobulin ; Drug: CsA; CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.; Other Names: Cyclosporine
Experimental: 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).	Drug: Campath-1H; Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).; Other Names: Alemtuzumab

Outcome Measures

Primary Outcome Measures

1. Participants no Longer Meeting Criteria for Severe Aplastic Anemia. [6 months]

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

Secondary Outcome Measures

1. Number of Participants With Robust Hematologic Recovery With Reticulocyte or Platelet Count [6 months]

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

2. Percentage of Cumulative Incidence of Relapse in Participants [3 year]

   Percentage of cumulative incidence of relapse of disease in participants

3. Percentage of Cumulative Incidence of Clonal Evolution in Participants [3 years]

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

4. Percentage of Participants no Longer Meeting Criteria for Severe Aplastic Anemia. [3 months and 6 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Severe aplastic anemia confirmed at NIH by:

Bone marrow cellularity less than 30% (excluding lymphocytes)

At least two of the following:

Absolute neutrophil count less than 500/microL;

Platelet count less than 20,000/ microL;

Reticulocyte count less than 60,000/ microL.

Severe aplastic anemia refractory to prior course(s) of h-ATG/CsA defined after 3 months from treatment with less or equal to 4 years from receiving h-ATG.

OR

Suboptimal response to initial immunosuppression with h-ATG/CsA as defined by platelet and reticulocyte count less than 50,000 /microL at 3 months.

Age greater than or equal to 2 years of age

EXCLUSION CRITERIA:

Diagnosis of Fanconi anemia.

Evidence of a clonal disorder on cytogenetics. Patients with super severe neutropenia (ANC less than 200/microL) will not be excluded initially if results of cytogenetics are not available or pending. If evidence of a clonal disorder is later identified, the subject will go off study.

Prior treatment courses with rabbit ATG or high dose cyclophosphamide (200 mg/kg or equivalent).

Infection not adequately responding to appropriate therapy.

Underlying immunodeficiency state including seropositivity for HIV.

Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old Man's Beard) within two weeks of enrollment.

Previous hypersensitivity to Campath-1H or its components.

Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy or that death within 7-10 days is likely.

Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible.

Serum creatinine greater than 2.5 mg/dL.

Current pregnancy or lactation or unwillingness to take contraceptives.

Inability to understand the investigational nature of the study or give informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Danielle M Townsley, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Mathé G, Amiel JL, Schwarzenberg L, Choay J, Trolard P, Schneider M, Hayat M, Schlumberger JR, Jasmin C. Bone marrow graft in man after conditioning by antilymphocytic serum. Br Med J. 1970 Apr 18;2(5702):131-6.
• Stein RS, Means RT Jr, Krantz SB, Flexner JM, Greer JP. Treatment of aplastic anemia with an investigational antilymphocyte serum prepared in rabbits. Am J Med Sci. 1994 Dec;308(6):338-43.
• Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. Review.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00065260
• Other Study ID Numbers: 030249; 03-H-0249
• First Posted: Jul 21, 2003
• Last Update Posted: Jul 21, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Alemtuzumab (Campath-1H); Rabbit ATG; Severe Aplastic Anemia; Cyclosporine; Thrombocytopenia; Leukopenia; Neutropenia; Autoimmunity; Relapse; Anemia
• Additional relevant MeSH terms: Anemia; Anemia, Aplastic; Cyclosporine; Alemtuzumab; Cyclosporins; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)
Arm/Group Description	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.	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).
Period Title: Overall Study
STARTED	27	27
COMPLETED	27	26
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	27	27	54
Age (Count of Participants)
<=18 years	3 11.1%	9 33.3%	12 22.2%
Between 18 and 65 years	22 81.5%	14 51.9%	36 66.7%
>=65 years	2 7.4%	4 14.8%	6 11.1%
Sex: Female, Male (Count of Participants)
Female	11 40.7%	13 48.1%	24 44.4%
Male	16 59.3%	14 51.9%	30 55.6%
Region of Enrollment (participants) [Number]
United States	27 100%	27 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Participants no Longer Meeting Criteria for Severe Aplastic Anemia.
Description	Number of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)
Arm/Group Description	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.	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).
Measure Participants	27	26
No Response	18 66.7%	17 63%
Partial Response	9 33.3%	9 33.3%
Complete Response	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Robust Hematologic Recovery With Reticulocyte or Platelet Count
Description	Number of participants with robust hematologic recovery with reticulocyte or platelet count ≥ 50,000/uL
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)
Arm/Group Description	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.	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).
Measure Participants	27	26
Count of Participants [Participants]	9 33.3%	9 33.3%

3. Secondary Outcome

Title	Percentage of Cumulative Incidence of Relapse in Participants
Description	Percentage of cumulative incidence of relapse of disease in participants
Time Frame	3 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)
Arm/Group Description	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.	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).
Measure Participants	27	26
Number [percentage of cumulative incidence]	19	9

4. Secondary Outcome

Title	Percentage of Cumulative Incidence of Clonal Evolution in Participants
Description	Percent of cumulative incidence of clonal evolution in participants to either paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia or acute leukemia.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)
Arm/Group Description	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.	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).
Measure Participants	27	26
Number [Percentage of Cumulative Incidence]	16	5

5. Secondary Outcome

Title	Percentage of Participants no Longer Meeting Criteria for Severe Aplastic Anemia.
Description	Percentage of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment
Time Frame	3 months and 6 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	r-ATG /Cyclosporine	Alemtuzumab (Campath-1H)
Arm/Group Description	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.	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).
Measure Participants	27	26
3 Months	19 70.4%	19 70.4%
6 Months	33 122.2%	37 137%

Adverse Events

Time Frame	3 years
Arm/Group Title	r-ATG /Cyclosporine		Alemtuzumab (Campath-1H)
Arm/Group Description	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.		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).
All Cause Mortality
	r-ATG /Cyclosporine		Alemtuzumab (Campath-1H)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/27 (33.3%)		4/27 (14.8%)
Serious Adverse Events
	r-ATG /Cyclosporine		Alemtuzumab (Campath-1H)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/27 (25.9%)		12/27 (44.4%)
Immune system disorders
infection	7/27 (25.9%)	7	12/27 (44.4%)	12
Other (Not Including Serious) Adverse Events
	r-ATG /Cyclosporine		Alemtuzumab (Campath-1H)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/27 (25.9%)		12/27 (44.4%)
Blood and lymphatic system disorders
infection	7/27 (25.9%)	7	12/27 (44.4%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.