Rituximab to Treat Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia

August 20, 2018 updated by: Adrian Wiestner, M.D., National Heart, Lung, and Blood Institute (NHLBI)

A Pilot Study of Recombinant Humanized Anti- Cluster of Differentiation Antigen 20 (Anti-CD20) Antibody (Rituximab) in Patients With Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia

This study will test whether the immune-suppressing drug rituximab can increase blood counts and reduce the need for transfusions in patients with moderate aplastic anemia, pure red cell aplasia, or Diamond Blackfan anemia. These are rare and serious blood disorders in which the immune system turns against bone marrow cells, causing the bone marrow to stop producing red blood cells in patients with pure red cell aplasia and Diamond Blackfan anemia, and red blood cells, white blood cells and platelets in patients with aplastic anemia. Rituximab is a laboratory-made monoclonal antibody that recognizes and destroys white blood cells called lymphocytes that are responsible for destroying bone marrow cells in these diseases. The drug is currently approved by the Food and Drug Administration for treating patients with B-cell non-Hodgkin lymphoma, a disease of white blood cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will test whether the immune-suppressing drug rituximab can increase blood counts and reduce the need for transfusions in patients with moderate aplastic anemia, pure red cell aplasia, or Diamond Blackfan anemia. These are rare and serious blood disorders in which the immune system turns against bone marrow cells, causing the bone marrow to stop producing red blood cells in patients with pure red cell aplasia and Diamond Blackfan anemia, and red blood cells, white blood cells and platelets in patients with aplastic anemia. Rituximab is a laboratory-made monoclonal antibody that recognizes and destroys white blood cells called lymphocytes that are responsible for destroying bone marrow cells in these diseases. The drug is currently approved by the Food and Drug Administration for treating patients with B-cell non-Hodgkin lymphoma, a disease of white blood cells.

Participants receive four doses of rituximab, once a week for 4 weeks through a needle in an arm vein. The infusion rate depends on how well the patient tolerates the drug. The first infusion usually takes 4 to 6 hours and the rest take 3 to 4 hours. The first and fourth infusions are given at NIH; the second and third may be given at NIH or by a patient's referring doctor. Patients who respond to rituximab but then relapse may receive one additional course of four doses. Patients may continue with transfusions and their current medications, including growth factors (e.g., Epogen and Neupogen) while on study, but may have to stop taking immunosuppressive drugs, such as prednisone or cyclosporine. Patients who must start another immunosuppressive medication are taken off rituximab and followed for safety with clinic visits one week and then once a month for 6 months after the first dose of rituximab.

Patients have a blood test once a week while receiving rituximab to evaluate blood counts. After treatment is completed, patients are evaluated once a month until 6 months, then once a year until 3 years to monitor the response to treatment and any drug side effects. Patients are evaluated at NIH for the 3- and 6-month visits and the annual visits. They may be seen at NIH or by their referring doctors for the 1-, 2-, 4- and 5-month visits. A blood test is done at every visit, and a bone marrow aspiration and biopsy are done at the 3-month visit (and when clinically needed to evaluate the effect of rituximab on bone marrow cells).

Study Type

Interventional

Enrollment (Actual)

11

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

7 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

Diagnosis of acquired moderate aplastic anemia defined as aplastic anemia (hypocellular bone marrow) and no evidence for an underlying disease process and depression of at least two out of three blood counts below these values:

  • Absolute neutrophil count (ANC) equal to or less than l200/mm(3)
  • platelet count equal to or less than 70,000/mm(3)
  • anemia with hemoglobin equal to or less than 8.5 g/dl or absolute reticulocyte count equal to or less than 60,000/mm(3) in transfusion-dependent patients but not fulfilling the criteria for severe disease defined by bone marrow cellularity less than 30% (excluding lymphocytes) and depression of at least two of the three peripheral counts:
  • ANC equal to or less than 500/ul
  • platelet count equal to or less than 20,000/ul
  • reticulocyte count less than 60,000/ul

Or

Diagnosis of pure red cell aplasia or Diamond Blackfan anemia requiring red blood cell (RBC) transfusions

Pure red cell aplasia is defined by

  • anemia,
  • reticulocytopenia (reticulocyte count equal to or less than 50,000/ mm(3))
  • and absent or decreased marrow erythroid precursors

Diamond Blackfan anemia is defined by

  • anemia,
  • reticulocytopenia (reticulocyte count equal to or less than 50,000/ mm(3))
  • and absent or decreased marrow erythroid precursors diagnosed at an early age

Because this population is prone to dry bone marrow aspirates, subjects from whom sufficient bone marrow cannot be collected for the evaluation of cellularity will not be excluded provided they meet all other inclusion criteria based on peripheral blood counts.

Pure Red cell Aplasia and Diamond Blackfan patients must be age greater than or equal to 2 years old and weight greater than 12 kg; Moderate Aplastic anemia patients must be age greater than or equal to 18.

Refractory to at least 1 course of immunosuppressive therapy or relapsed disease after prior immunosuppressive therapy (PRCA/DBA patients only).

Patients or their parent(s)/responsible guardian(s) must be able to comprehend and be willing to sign an informed consent.

EXCLUSION CRITERIA:

Current diagnosis of Fanconi's anemia or other congenital bone marrow failure syndromes except for DBA

History of a cytogenetic abnormality indicating myelodysplasia (MDS)

Active infection not adequately responding to appropriate therapy

HIV positivity

Positive anti- hepatitis B core antibody (antiHBc) or HBsAG

History of clinically significant arrhythmia

Known anaphylaxis or immunoglobulin E (IgE) mediated hypersensitivity to murine proteins or to any component of this product.

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 the next month is likely

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

History of recent or ongoing B19 parvovirus infection

Psychiatric, affective, or other disorder that may compromise the ability to give informed consent or to cooperate in a research study.

Pregnancy or lactation or unwillingness to take contraceptives

Participation in any other investigational drug trial or exposure to other investigational agents (other than hematopoietic growth factors) within 30 days of study entry. Use of low dose immunosuppressive agents may continue at the PIs discretion provided that the patient has been taking this drug for at least 3 months.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab (Rituxan)
This is a non-randomized, off label, pilot study of humanized anti CD20 rituximab (Rituxan®) in patients with moderate aplastic anemia, pure red cell aplasia or Diamond-Blackfan anemia who have either failed to respond to at least one prior course of immunosuppressive therapy (PRCA/DBA patients only)or who have relapsed disease after prior immunosuppressive therapy (PRCA/DBA patients only).
Drug: Rituximab
Rituximab (Rituxan) 375mg/m2 intravenous infusion. The infusion will be once every week for a total of 4 doses.
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response to Rituximab
Time Frame: 6 months

Rituximab will be given to moderate aplastic anemia (MAA), pure red cell aplasia or Diamond Blackfan anemia subjects. Rituxmiab will be given to evaluate if these bone marrow failure syndrome subjects will have an immune response to the intervention. The subjects will receive 375 mg/ meters squared of rituximab which will be infused intravenously once evey week for a total of 4 doses.

Primary endpoint will determine immune response by evaluating changes in peripheral blood counts (platelets, absolute neutrophil count, reticulocyte count, hemoglobin) and transfusion requirements at 6 months. The response wil be will be categorized as complete, partial or no response. Subjects will be categorized as complete responders if their blood counts return to normal. Subjects will categorized as partial responders if there is an improvement in 2 or 3 of the depressed baseline blood counts.
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Response Assessment at 3 Months
Time Frame: 3 months
3 months
Response Rates at 12 Months (After the First Dose of Study Med)
Time Frame: 12 months
12 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)

Investigators

  • Principal Investigator: Sabrina Martyr, MD, NIH National Heart, Lung and Blood Institute

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 1, 2005

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

September 29, 2005

First Submitted That Met QC Criteria

September 28, 2005

First Posted (Estimate)

September 29, 2005

Study Record Updates

Last Update Posted (Actual)

September 18, 2018

Last Update Submitted That Met QC Criteria

August 20, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 050244
  • 05-H-0244 (Other Identifier: NIH NHLBI)

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.

Clinical Trials on Anemia, Aplastic

Clinical Trials on Rituximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe