Thrombotic Thrombocytopenic PurpuraPhase 2NCT01554514
Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
A Phase 2 study testing rituximab in people with Thrombotic Thrombocytopenic Purpura, run by Washington University School of Medicine at 4 sites in United States.
Trial summary
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots throughout the body that can damage major organs and cause death. TTP is treated with plasma exchange (also called "plasmapheresis"). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombotic Thrombocytopenic Purpura
- 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
- 19 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2012to 14 Feb 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or greater
- Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
- Platelet count of < 80,000 for newly diagnosed patients and < 120,000 for relapsed patients
- Microangiopathic hemolytic anemia with RBC fragmentation
- LDH >1 x ULN
- Subjects who will receive treatment for TTP with plasma exchange
- Subjects who have not started the 5th plasma exchange
- Plasma ADAMTS13 activity <10%
Who cannot join
- Treatment for TTP within the past 2 months
- Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli O157:H7 or related organism
- Currently under treatment for cancer (subjects with localized skin carcinoma will be accepted)
- Microangiopathic hemolytic anemia due to a mechanical heart valve
- Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or papilledema
- Organ or stem cell transplant
Show all 17Show fewer
- Use of calcineurin inhibitors (sirolimus, tacrolimus, cyclosporin A) within 6 months prior to diagnosis of TTP
- Disseminated intravascular coagulation as defined by:
- INR >2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen <100 mg/dl
- Pregnancy
- Known congenital TTP.
- Rituximab within the previous year.
- HIV history or positive serology
- History of hepatitis B or positive serology for HBsAg or Anti-HBc
- Persistent or unexplained platelet count below 150,000/μL within 3 months of current TTP presentation
- Hypersensitivities or allergies to murine and/or humanized antibodies
- Current participation in trials of investigational therapies or devices, other than central catheters
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30322
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Duke University Medical Center
Durham, North Carolina, 27710
Washington University
St Louis, Missouri, 63110
About this study
Official title: Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots throughout the body that can damage major organs and cause death. TTP is treated with plasma exchange (also called "plasmapheresis"). Patients who do not respond initially to plasma exchange often are helped by later treatment with rituximab. The purpose of this study is to see whether combining low doses of rituximab with plasma exchange will help patients get better sooner and reduce the chance of getting TTP again.
Read the detailed description
This is a pilot safety/efficacy study of adjuvant low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for the treatment of thrombotic thrombocytopenic purpura (TTP) with severe ADAMTS13 deficiency. Results for study subjects will be compared to historical controls treated initially with plasma exchange and corticosteroids. This study proposes to test the hypothesis that adjuvant low dose rituximab may decrease the incidence of a composite primary endpoint (exacerbations or refractory disease) in acquired TTP with severe ADAMTS13 deficiency. A novel ADAMTS13 assay will be used to identify patients with TTP and severe ADAMTS13 deficiency for enrollment, and to assess the utility of ADAMST13 as a biomarker for response to therapy and prognosis.
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Being tested
- rituximab
- Keywords
- ADAMTS13, Rituximab, Thrombotic thrombocytopenic purpura, TTP, Plasma exchange
- Medical subject headings
- Purpura, Thrombotic Thrombocytopenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
Also called Rituxan
rituximab intravenously 100 mg every week for four doses
| Study group | Role | What they receive |
|---|---|---|
| low dose rituximab | Experimental | this is a single-arm trial Receives: Biological: rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP
Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60.
Measured: 60 days
Secondary outcomes (6)
Incidence of Durable Treatment Response
Treatment Response is 2 consecutive days with platelet count ≥150, 000/µL Durable Treatment Response is a Treatment Response that persists for ≥30 days after discontinuation of plasma exchange and includes those with exacerbations
Measured: 60 days
Number of Days to Durable Treatment Response
Median time to treatment response
Measured: 60 days
Incidence of Relapse
Relapse is recurring TTP >30 days after Treatment Response
Measured: Between 30 days and 2 years
Months to Relapse
Mean months to relapse
Measured: 2 years
Incidence of Death
Incidence of death will be assessed at 4 weeks, 1 year and 2 years
Measured: 2 years
Treatment-related Adverse Events
Incidence, type and severity of treatment-related adverse events will be assessed. Patient reports, lab values, and physical exam were used to identify treatment-related adverse events.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2012 (estimated)
- Study startAug 2012
- Primary completion14 Feb 2020
- Study completion14 Feb 2020
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 (5)Papers the sponsor has linked to this study.
- Other trials for Thrombotic Thrombocytopenic PurpuraStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Elaine M Majerus, MD, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01554514
- Sponsor's protocol ID
- 201108256-LDrituximab
- Other IDs
- 1U54HL112303-01
- Status last verified
- Aug 2021
- First submitted
- 8 Mar 2012
- Last updated
- 17 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Froissart A, Buffet M, Veyradier A, Poullin P, Provot F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. doi: 10.1097/CCM.0b013e31822e9d66.
PubMed 21926591Kiss JE. Thrombotic thrombocytopenic purpura: recognition and management. Int J Hematol. 2010 Jan;91(1):36-45. doi: 10.1007/s12185-009-0478-z.
PubMed 20058208Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013 Mar;11(3):481-90. doi: 10.1111/jth.12114.
PubMed 23279219Ahmad A, Aggarwal A, Sharma D, Dave HP, Kinsella V, Rick ME, Schechter GP. Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol. 2004 Oct;77(2):171-6. doi: 10.1002/ajh.20166.
PubMed 15389904Chemnitz J, Draube A, Scheid C, Staib P, Schulz A, Diehl V, Sohngen D. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab. Am J Hematol. 2002 Oct;71(2):105-8. doi: 10.1002/ajh.10204.
PubMed 12353309
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
- ClinicalTrials.gov ID
- NCT01554514
- Acronym / sponsor ID
- 201108256-LDrituximab
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Keywords
- ADAMTS13, Rituximab, Thrombotic thrombocytopenic purpura, TTP, Plasma exchange
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Aug 2012
- Primary completion
- 14 Feb 2020 (actual)
- Study completion
- 14 Feb 2020 (actual)
- First posted
- 15 Mar 2012 (estimated)
- Results
- Posted 13 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots throughout the body that can damage major organs and cause death. TTP is treated with plasma exchange (also called "plasmapheresis"). Patients who do not respond initially to plasma exchange often are helped by later treatment with rituximab. The purpose of this study is to see whether combining low doses of rituximab with plasma exchange will help patients get better sooner and reduce the chance of getting TTP again.
Detailed description
This is a pilot safety/efficacy study of adjuvant low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for the treatment of thrombotic thrombocytopenic purpura (TTP) with severe ADAMTS13 deficiency. Results for study subjects will be compared to historical controls treated initially with plasma exchange and corticosteroids. This study proposes to test the hypothesis that adjuvant low dose rituximab may decrease the incidence of a composite primary endpoint (exacerbations or refractory disease) in acquired TTP with severe ADAMTS13 deficiency. A novel ADAMTS13 assay will be used to identify patients with TTP and severe ADAMTS13 deficiency for enrollment, and to assess the utility of ADAMST13 as a biomarker for response to therapy and prognosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| low dose rituximab | Experimental | Biological: rituximabthis is a single-arm trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 or greater
- Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
- Subjects who will receive treatment for TTP with plasma exchange
- Subjects who have not started the 5th plasma exchange
- Plasma ADAMTS13 activity <10%
Key exclusion criteria (17 listed)
- Treatment for TTP within the past 2 months
- Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli O157:H7 or related organism
- Currently under treatment for cancer (subjects with localized skin carcinoma will be accepted)
- Microangiopathic hemolytic anemia due to a mechanical heart valve
- Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or papilledema
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 intravenously 100 mg every week for four doses | Biological | low dose rituximab |
Primary outcome
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP
Time frame: 60 days
Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60.
6 secondary outcomes
Incidence of Durable Treatment Response
Time frame: 60 days
Number of Days to Durable Treatment Response
Time frame: 60 days
Incidence of Relapse
Time frame: Between 30 days and 2 years
Months to Relapse
Time frame: 2 years
Incidence of Death
Time frame: 2 years
Treatment-related Adverse Events
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21926591Froissart A, Buffet M, Veyradier A, Poullin P, Provot F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. doi: 10.1097/CCM.0b013e31822e9d66.
- Results publication: PubMed 20058208Kiss JE. Thrombotic thrombocytopenic purpura: recognition and management. Int J Hematol. 2010 Jan;91(1):36-45. doi: 10.1007/s12185-009-0478-z.
- Results publication: PubMed 23279219Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013 Mar;11(3):481-90. doi: 10.1111/jth.12114.
- Results publication: PubMed 15389904Ahmad A, Aggarwal A, Sharma D, Dave HP, Kinsella V, Rick ME, Schechter GP. Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol. 2004 Oct;77(2):171-6. doi: 10.1002/ajh.20166.
- Results publication: PubMed 12353309Chemnitz J, Draube A, Scheid C, Staib P, Schulz A, Diehl V, Sohngen D. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab. Am J Hematol. 2002 Oct;71(2):105-8. doi: 10.1002/ajh.10204.
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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.
Elaine M Majerus, MD, PhD principal investigator
Washington University School of Medicine
4 sites 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 Thrombotic Thrombocytopenic Purpura, run by Washington University School of Medicine at 4 sites 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 8 inclusion and 17 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 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 13 Aug 2021). 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?
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP (time frame: 60 days). 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 NCT01554514, which also lists 5 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 17 Aug 2021.