Phase III Randomized Study of Cyclophosphamide With or Without Antithymocyte Globulin Before Bone Marrow Transplantation in Patients With Aplastic Anemia

Roswell Park Comprehensive Cancer Center

Status and phase: Completed; Phase 3

Conditions: Aplastic Anemia

Treatments: Drug: Cyclophosphamide; Procedure: Bone marrow transplantation; Drug: Anti-thymocyte globulin

Study type: Interventional

Funder types: Other

Identifiers

NCT00004474

RPCI-RP-9804

NCI-G98-1491

199/14004

IBMTR-1

Details and patient eligibility

About

OBJECTIVES:

I. Compare outcome, including graft failure, graft versus host disease, and survival of HLA-identical sibling bone marrow transplants for aplastic anemia using cyclophosphamide with or without antithymocyte globulin as a conditioning regimen.

Full description

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to receive cyclophosphamide IV over 60 minutes on days -5 to -2 with or without antithymocyte globulin IV over 4 hours.

All patients then receive bone marrow over 60-120 minutes on day 0, 36 hours after the last dose of cyclophosphamide.

Patients are followed at day 100, at 6 months, and at 1 year posttransplant.

Sex: All

Ages: Under 59 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Severe aplastic anemia with the following criteria:

Hypocellular bone marrow with cellularity less than 20%

At least 2 of the following hematologic abnormalities:

• Neutrophil count no greater than 500/mm3
• Platelet count no greater than 20,000/mm3
• Reticulocyte count no greater than 50,000/mm3

HLA-identical sibling donor available

No clonal cytogenetic abnormalities, paroxysmal nocturnal hemoglobinuria, or myelodysplastic syndrome within 3 months of diagnosis of aplastic anemia

No congenital or constitutional aplastic anemia or Fanconi anemia

--Patient Characteristics--

Hepatic: Bilirubin less than 3 times upper limit of normal (ULN)

Renal: Creatinine less than 2 times ULN

Cardiovascular: Normal cardiac function

Other:

• No uncontrolled infection
• No severe concurrent disease
• HIV negative
• Fertile patients must use effective contraception

Trial design

224 participants in 2 patient groups

1

Experimental group

Description:

Participants will receive cyclophosphamide IV over 60 minutes on Days -5 to -2 with antithymocyte globulin IV over 4 hours; then, after the last does cycophosphamide, participants will receive a bone marrow transplant over 60 to 120 minutes on Day 0.

Treatment:

Procedure: Bone marrow transplantation

Drug: Anti-thymocyte globulin

Drug: Cyclophosphamide

2

Experimental group

Description:

Participants will receive cyclophosphamide IV over 60 minutes on Days -5 to -2; then, after the last does cycophosphamide, participants will receive a bone marrow transplant over 60 to 120 minutes on Day 0.

Treatment:

Procedure: Bone marrow transplantation

Drug: Cyclophosphamide