Anemia, AplasticPhase 2NCT00229619
Rituximab to Treat Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia
A Phase 2 study testing Rituximab in people with Anemia, Aplastic and Red-Cell Aplasia, Pure, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Anemia, Aplastic, Red-Cell Aplasia, Pure, Anemia, Diamond-Blackfan
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 21Show fewer
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read the 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).
- Being tested
- Rituximab
- 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
- Medical subject headings
- Anemia, Aplastic, Red-Cell Aplasia, Pure, Anemia, Diamond-Blackfan, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
Rituximab (Rituxan) 375mg/m2 intravenous infusion. The infusion will be once every week for a total of 4 doses.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
Response Assessment at 3 Months
Measured: 3 months
Response Rates at 12 Months (After the First Dose of Study Med)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anemia, AplasticStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Adrian Wiestner, M.D., National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Sabrina Martyr, MD, Principal investigator, NIH National Heart, Lung, and Blood Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00229619
- Sponsor's protocol ID
- 050244
- Other IDs
- 05-H-0244
- Status last verified
- Aug 2018
- First submitted
- 29 Sep 2005
- Last updated
- 18 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 15689912Gottenberg 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.
PubMed 15550531Edwards 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.
PubMed 15201414
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00229619
- Acronym / sponsor ID
- 050244
- Keywords
- rituxan, Immunosuppression, Bone Marrow Failure, Monoclonal Antibody Therapy, Diamond Blackfan Anemia (DBA), T -Cells, B-Cells, Hematopoiesis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Sep 2005
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 29 Sep 2005 (estimated)
- Results
- Posted 28 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab (Rituxan) | Experimental | Drug: RituximabThis 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). |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: RituxanRituximab (Rituxan) 375mg/m2 intravenous infusion. The infusion will be once every week for a total of 4 doses. | Drug | Rituximab (Rituxan) |
Primary outcome
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.
2 secondary outcomes
Response Assessment at 3 Months
Time frame: 3 months
Response Rates at 12 Months (After the First Dose of Study Med)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15689912Wang 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.
- Background: PubMed 15550531Gottenberg 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.
- Background: PubMed 15201414Edwards 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabrina Martyr, MD principal investigator
NIH National Heart, Lung, and Blood Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Anemia, Aplastic and Red-Cell Aplasia, Pure, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to Rituximab (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00229619, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2018.