Alemtuzumab to Treat Severe Aplastic Anemia

NCT00195624 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 05024205-H-0242
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and usefulness of a new immunosuppressive drug, alemtuzumab (Campath ), in patients with severe aplastic anemia (SAA). SAA is a rare and serious blood disorder in which the bone marrow stops making red blood cells, white blood cells and platelets. Alemtuzumab is a monoclonal antibody that attaches to and kills white blood cells called lymphocytes. In certain types of aplastic anemia, lymphocytes are responsible for the destruction of stem cells in the bone marrow, leading to a decrease in blood counts. Because alemtuzumab destroys lymphocytes, it may be effective in treating aplastic anemia. Alemtuzumab is currently approved to treat chronic lymphocytic leukemia and is also helpful in other conditions that require immunosuppression, such as rheumatoid arthritis and immune cytopenias. Patients 2 years of age and older with severe aplastic anemia whose disease does not respond to immunosuppressive therapy or has recurred following immunosuppressive therapy may be eligible for this study. Participants undergo the following tests and procedures:

• Pretreatment evaluation: Patients have a medical history, physical examination, blood tests, electrocardiogram (EKG), echocardiogram, 24-hour Holter monitor (continuous 24-hour monitoring of electrical activity of the heart), bone marrow biopsy (withdrawal through a needle of a small sample of bone marrow for analysis).
• Placement of a central line, if needed: An intravenous line (tube) is placed into a major vein in the patient's chest. It can stay in the body for the entire treatment period and be used to give chemotherapy or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples.
• Alemtuzumab therapy: Patients are admitted to the NIH Clinical Center for the first few injections for close monitoring of side effects. After receiving an initial small test dose, patients begin the first of ten daily injections under the skin, each lasting about 2 hours. Once patients tolerate the infusions with minimal or no side effects, they may be given the remaining infusions on an outpatient basis. Patients who relapse after their initial response to alemtuzumab are given cyclosporine to see if this drug will boost their immune response.
• Patients receive transfusions, growth factors, and antibiotic therapy, as needed.
• Infection therapy: Patients are given aerosolized pentamidine to protect against lung infections and valacyclovir to protect against herpes infections.
• A blood test is done and vital signs are measured every day while patients receive alemtuzumab.
• Patients have an echocardiogram and 24-hour Holter monitor after the last dose of alemtuzumab.
• Blood tests are done weekly for the first 3 months after alemtuzumab administration, then every other week until 6 months. Patients return to the NIH for follow-up visits 1 month, 3 months, 6 months, and yearly for 5 years after the last dose of alemtuzumab for the following tests and evaluations:
• Blood test
• Repeat echocardiogram at 3-month visit
• Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab, then as clinically indicated for 5 years.

Conditions

Severe Aplastic Anemia, Refractory; Severe Aplastic Anemia, Relapse

Keywords

Immunosuppression; T-cells; Hematopoiesis; Autoimmunity; Thrombocytopenia; Severe Aplastic Anemia; SAA

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hematological Response at 6 Months

  Hematological response is defined as no longer satisfying blood count criteria for Severe Aplastic Anemia. Patients were classified as responders if they met two of the following three criteria: ANC greater than 500/ mm'; platelet count greater than 20,000/mm3; and reticulocyte count greater than 40,000/mm3 (60,000/mm3 after January 1993).

  6 months

Study Arms (3)

Relapsed severe aplastic anemia

EXPERIMENTAL

Subjects diagnosed with relapsed severe aplastic anemia

Biological: Alemtuzumab (Campath )

Refractory severe asplastic anemia

EXPERIMENTAL

Subjects diagnosed with refractory severe aplastic anemia

Biological: Alemtuzumab (Campath )

Relapse after Alemtuzumab

EXPERIMENTAL

Subjects who relapse after initial response to alemtuzumab therapy will have cyclosporine added to the regimen after the 6 month visit.

Drug: Cyclosporine

Interventions

Alemtuzumab (Campath ) BIOLOGICAL

Campath administered at a dose of 10/mg/day for 10 days

Refractory severe asplastic anemia; Relapsed severe aplastic anemia

Cyclosporine DRUG

Subjects who relapse after initial response to alemtuzumab therapy will have cyclosporine added to the regimen after the 6 month visit. Dosing will be based on ideal body weight and will be adjusted to maintain a target level of 200 - 400 ng /ml.

Relapse after Alemtuzumab

Eligibility Criteria

• Age: 2 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed severe aplastic anemia after initial hematologic response to a prior course of h-ATG or r-ATG based immunosuppression
• Refractory severe aplastic anemia not responding to both horse-ATG and rabbit ATG-based immunosuppression
• The criteria for severe aplastic anemia are two of the three criteria:
• Absolute neutrophil count less than or equal to 500 /mm(3)
• Platelets to less than or equal to 20,000/mm(3)
• Absolute reticulocyte count less than 60,000 /microL
• Age greater than or equal to 2 years old and greater than 12 kg
• Prospective subjects or their parent(s)/responsible guardian(s) must be able to comprehend and be willing to sign an informed consent.

You may not qualify if:

• Known Diagnosis of Fanconi's anemia
• Evidence of a clonal disorder on cytogenetics. In the refractory disease setting, prospective subjects with super severe neutropenia (ANC less than 200 /microL) will not be excluded if results of cytogenetics are not available or pending.
• Infection not adequately responding to appropriate therapy
• HIV positivity
• Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old Man's Beard) within 2 weeks of enrollment
• 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
• Previous hypersensitivity to alemtuzumab or its components
• Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible
• Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
• Not able to understand the investigational nature of the study or give informed consent

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 (7)

• Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.

  PMID: 7780125 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

• Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.

  PMID: 2981406 BACKGROUND

• Aggarwal N, Manley AL, Shalhoub R, Durrani J, Rios O, Lotter J, Patel BA, Wu CO, Young NS, Groarke EM. Alemtuzumab in relapsed immune severe aplastic anemia: Long-term results of a phase II study. Am J Hematol. 2023 Jun;98(6):932-939. doi: 10.1002/ajh.26924. Epub 2023 Apr 6.

  PMID: 37021397 DERIVED

• 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

• Pang Y, Xiao HW, Zhang H, Liu ZH, Li L, Gao Y, Li HB, Jiang ZJ, Tan H, Lin JR, Du X, Weng JY, Nie DN, Lin DJ, Zhang XZ, Liu QF, Xu DR, Chen HJ, Ge XH, Wang XY, Xiao Y. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial. Stem Cells Transl Med. 2017 Jul;6(7):1569-1575. doi: 10.1002/sctm.16-0227. Epub 2017 May 15.

  PMID: 28504860 DERIVED

• Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Wu CO, Young NS. Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. Blood. 2012 Jan 12;119(2):345-54. doi: 10.1182/blood-2011-05-352328. Epub 2011 Nov 8.

  PMID: 22067384 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Recurrence; Autoimmune Diseases; Thrombocytopenia

Interventions

Alemtuzumab; Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Results Point of Contact

• Title: Young, Neal
• Organization: National Heart Lung and Blood Institute

youngns@mail.nih.gov

+1 301 496 5093

Study Officials

• Neal S Young, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: September 16, 2005
• First Posted: September 19, 2005
• Study Start: September 15, 2005
• Primary Completion: April 14, 2014
• Study Completion: October 15, 2018
• Last Updated: July 7, 2020
• Results First Posted: August 2, 2019

Record last verified: 2018-10

Locations

US (1)