Alemtuzumab to Treat Severe Aplastic Anemia

June 29, 2020 updated by: National Heart, Lung, and Blood Institute (NHLBI)

A Pilot Study of Alemtuzumab (Campath) in Patients With Relapsed or Refractory Severe Aplastic Anemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hematopoietic stem cell destruction in many human bone marrow failure syndromes is now recognized to be secondary to immune mechanisms. Severe aplastic anemia (SAA) is a life-threatening blood disease which can be effectively treated with immunosuppressive drug regimens. However, a significant minority of patients with SAA fail to respond to a single course of horse antithymocyte globulin and cyclosporine, and other patients experience relapse, especially on discontinuation of therapy. Pancytopenia secondary to refractory or relapsed aplastic anemia has a poor prognosis, with death usually resulting from infectious complications. Alemtuzumab (Campath ) is a humanized IgG1 monoclonal antibody directed against the CD52 protein; CD52 is expressed on all lymphocytes and monocytes. Alemtuzumab (Campath ) produces profound and persistent lymphopenia. The antibody has been used to treat a wide range of autoimmune diseases, lymphoid malignancies, and in solid organ and hematopoietic stem cell transplantation. In our limited experience with alemtuzumab for the treatment of SAA refractory to horse antithymocyte globulin, meaningful hematologic responses have been observed and toxicity has been modest.

We therefore propose a non-randomized pilot phase II study of this humanized monoclonal antibody in SAA relapsed or refractory to ATG. Commercially available alemtuzumab (Campath ) will be administered at 10 mg per day subcutaneously for 10 days total.

The primary end point of the study is the response rate at 6 months, defined as no longer satisfying blood count criteria for SAA.

Relapse, robustness of the hematopoietic recovery at 3 and 6 months, 3 months responses, survival, and clonal evolution to myelodysplasia and acute leukemia will be secondary end points.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 110 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

Relapsed severe aplastic anemia after initial hematologic response to a prior course of h-ATG or r-ATG based immunosuppression

Or

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.

EXCLUSION CRITERIA:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Relapsed severe aplastic anemia
Subjects diagnosed with relapsed severe aplastic anemia
Biological: Alemtuzumab (Campath )
Campath administered at a dose of 10/mg/day for 10 days
Experimental: Refractory severe asplastic anemia
Subjects diagnosed with refractory severe aplastic anemia
Biological: Alemtuzumab (Campath )
Campath administered at a dose of 10/mg/day for 10 days
Experimental: Relapse after Alemtuzumab
Subjects who relapse after initial response to alemtuzumab therapy will have cyclosporine added to the regimen after the 6 month visit.
Drug: Cyclosporine
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Hematological Response at 6 Months
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 15, 2005

Primary Completion (Actual)

April 14, 2014

Study Completion (Actual)

October 15, 2018

Study Registration Dates

First Submitted

September 16, 2005

First Submitted That Met QC Criteria

September 16, 2005

First Posted (Estimate)

September 19, 2005

Study Record Updates

Last Update Posted (Actual)

July 7, 2020

Last Update Submitted That Met QC Criteria

June 29, 2020

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 050242
  • 05-H-0242

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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