Combination Therapy of Severe Aplastic Anemia

NCT00001964 | Completed Phase 2 FDA Drug

• 2 other identifiers: 00003200-H-0032
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the safety and effectiveness of a combination of three drugs in treating severe aplastic anemia and preventing its recurrence. Two drugs used in this trial ATG and cyclosporine are standard combination therapy for aplastic anemia. This study will try to improve this therapy in three ways: 1) by altering the drug regimen to allow the drugs to work better; 2) by reducing the risk of kidney damage; and 3) by adding a third drug mycophenolate mofetil to try to prevent disease relapse. Patients with severe aplastic anemia who do not have a suitable bone marrow donor or who decline bone marrow transplantation may participate in this study. Patients will have a skin test for ATG allergy, chest X-ray, blood test, and bone marrow aspiration before treatment begins. ATG will then be started, infused through a vein continuously for 4 days. Ten days after ATG is stopped, cyclosporine treatment will begin, taken twice a day by mouth in either liquid or capsule form and will continue for 6 months. Also, in the first 2 weeks of treatment, patients will be given a full dose of corticosteroid (prednisone) to prevent serum sickness that could develop as a side effect of ATG therapy. The dosage will be decreased after that. Mycophenolate will be started at the same time as ATG, in two daily doses by mouth, and will continue for 18 months. Patients will be hospitalized at the beginning of the study. During this time, blood will be drawn at 3-week intervals and a bone marrow examination will be repeated 3 months after treatment has begun. Additional tests, including X-rays may be required. After hospital discharge, patients will be followed on an outpatient basis at 3-month intervals. The patients own physician will perform blood tests weekly and kidney and liver function tests every 2 weeks during cyclosporine therapy. Transfusions may be required initially.

Conditions

Severe Aplastic Anemia

Keywords

Hematopoiesis; Bone Marrow Failure; Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• reduction in 24-month relapse

  reduction in 24-month relapse

  24 months

Study Arms (2)

single arm

EXPERIMENTAL

ATG 40 mg/kg/d for 4 d; CsA 2 weeks after at 12 mg/kg/d for 6 months. MMF starting on first day of ATG at 600 mg/m2 twice daily for 18 months

Drug: Cyclosporine A; Drug: ATG; Drug: MMF

single arm 2

EXPERIMENTAL

ATG at 40 mg/kg/day for 4 days; MMF at 600 mg/m2 twice daily for 18 months and CsA at 12 mg/kg/day for 6 months starting 2 weeks after ATG and MMF

Drug: Cyclosporine A; Drug: ATG; Drug: MMF

Interventions

Cyclosporine A DRUG

Cyclosporine A

single arm; single arm 2

ATG DRUG

ATG

single arm; single arm 2

MMF DRUG

MMF

single arm; single arm 2

Eligibility Criteria

• Age: 1 Year - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Only patients with SAA will be admitted, defined as:
• Bone marrow cellularity less than 30%.
• At least two of the following blood count findings: absolute granulocyte count less than 500/mm(3); platelet count less than 20,000/mm(3); reticulocyte count less than 60,000/mm(3).
• Age greater than or equal to 1 years.
• Weight greater than 12 kg.

You may not qualify if:

• Serum creatinine greater than 2 mg/dl or estimated creatinine clearance less than 40 ml/min.
• Underlying carcinoma, recent history of radiation or chemotherapy.
• Current pregnancy or unwillingness to be treated with oral contraceptives.
• Inability to comprehend the investigational nature of the study.
• Moribund status or concurrent hepatic, renal, cardiac, neurologic, or metabolic disease of such severity that death within 7 to 10 days is likely.
• Evidence of other etiology than AA for bone marrow failure, including positive clastogenic stress cytogenetic assay for Fanconi anemia and marrow chromosome abnormalities typical of myelodysplasia.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Young NS. Acquired aplastic anemia. JAMA. 1999 Jul 21;282(3):271-8. doi: 10.1001/jama.282.3.271. No abstract available.

  PMID: 10422997 BACKGROUND

• Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.

  PMID: 9134878 BACKGROUND

• Nimer SD, Ireland P, Meshkinpour A, Frane M. An increased HLA DR2 frequency is seen in aplastic anemia patients. Blood. 1994 Aug 1;84(3):923-7.

  PMID: 8043874 BACKGROUND

• Zaimoku Y, Patel BA, Adams SD, Shalhoub R, Groarke EM, Lee AAC, Kajigaya S, Feng X, Rios OJ, Eager H, Alemu L, Quinones Raffo D, Wu CO, Flegel WA, Young NS. HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia. Blood. 2021 Dec 30;138(26):2799-2809. doi: 10.1182/blood.2021012895.

  PMID: 34724566 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Bone Marrow Failure Disorders

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Neal S Young, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2000
• First Posted: January 19, 2000
• Study Start: March 17, 2000
• Primary Completion: December 9, 2003
• Study Completion: May 12, 2015
• Last Updated: March 16, 2021

Record last verified: 2021-03

Locations

US (1)