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

NCT00229619 | Completed Phase 2 Results DMC

• 2 other identifiers: 05024405-H-0244
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anemia, Aplastic; Red-Cell Aplasia, Pure; Anemia, Diamond-Blackfan

Keywords

rituxan; Immunosuppression; Bone Marrow Failure; Monoclonal Antibody Therapy; Diamond Blackfan Anemia (DBA); T -Cells; B-Cells; Hematopoiesis; Moderate Aplastic Anemia (MAA); Diamond-Blackfan Anemia; DBA; Pure Red Cell Aplasia; PRCA

Outcome Measures

Primary Outcomes (1)

• Response to Rituximab

  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 Outcomes (2)

• Response Assessment at 3 Months

  3 months

• Response Rates at 12 Months (After the First Dose of Study Med)

  12 months

Study Arms (1)

Rituximab (Rituxan)

EXPERIMENTAL

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

Interventions

Rituximab DRUG

Rituximab (Rituxan) 375mg/m2 intravenous infusion. The infusion will be once every week for a total of 4 doses.

Also known as: Rituxan

Rituximab (Rituxan)

Eligibility Criteria

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

You may qualify if:

• 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
• 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))

You may not qualify if:

• 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.

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 (3)

• Wang J, Wiley JM, Luddy R, Greenberg J, Feuerstein MA, Bussel JB. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr. 2005 Feb;146(2):217-21. doi: 10.1016/j.jpeds.2004.09.004.

  PMID: 15689912 BACKGROUND

• Gottenberg JE, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A, Larroche C, Soubrier M, Bouillet L, Dougados M, Fain O, Farge D, Kyndt X, Lortholary O, Masson C, Moura B, Remy P, Thomas T, Wendling D, Anaya JM, Sibilia J, Mariette X; Club Rheumatismes et Inflammation (CRI). Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis. 2005 Jun;64(6):913-20. doi: 10.1136/ard.2004.029694. Epub 2004 Nov 18.

  PMID: 15550531 BACKGROUND

• Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81. doi: 10.1056/NEJMoa032534.

  PMID: 15201414 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Red-Cell Aplasia, Pure; Anemia, Diamond-Blackfan; Bone Marrow Failure Disorders

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Hypoplastic, Congenital; Congenital Bone Marrow Failure Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was terminated early due to slow accrual. Conclusions on efficacy limited by small sample size.

Results Point of Contact

• Title: Adrian Wiestner MD, NHLBI
• Organization: NIH National Heart, Lung and Blood Institute

wiestnera@nhlbi.nih.gov

301-594-6855

Study Officials

• Sabrina Martyr, MD

  NIH National Heart, Lung, and Blood Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: NHLBI Senior Investigator

Study Record Dates

• First Submitted: September 29, 2005
• First Posted: September 29, 2005
• Study Start: September 1, 2005
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: September 18, 2018
• Results First Posted: July 28, 2014

Record last verified: 2018-08

Locations

US (1)