AIHA - Warm Autoimmune Hemolytic AnemiaPhase 2ISRAELNCT03827603
Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia
A Phase 2 study testing Ibrutinib in people with AIHA - Warm Autoimmune Hemolytic Anemia, run by Eugene Nikitin at 1 site in Russia.
Trial summary
This is an open-labeled, single arm, Phase II, two staged study of combination of ibrutinib and rituximab in patients with autoimmune cytopenia and underlying CLL. In stage I (remission induction) patients will receive ibrutinib and rituximab for 6 months; in stage II (maintenance) - only ibrutinib until relapse… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AIHA - Warm Autoimmune Hemolytic Anemia
- What is being tested?
- Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteRussia
- Study dates
- 21 Feb 2017to 31 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to Visit 2
- Proven diagnosis autoimmune hemolytic anemia or pure red cell aplasia
- Relapse of AIHA/PRCA after steroids, splenectomy or rituximab or refractoriness to glucocorticosteroid hormones
- No more than 2 lines of antileukemia treatment
- Hematology values must be within the following limits:
- Absolute neutrophil count 1000/mm3 independent of growth factor support
Show all 17Show fewer
- Platelets 100.000/mm3 or 50.000/mm3 if bone marrow involvement independent of transfusion support in either situation
- Biochemical values within the following limits:
- Alanine aminotransferase and aspartate aminotransferase less 3 upper limit of normal (ULN)
- Total bilirubin less 1.5x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
- Serum creatinine less 2 x ULN or estimated Glomerular Filtration Rate more 40 mL/min/1.73 m2
- Age ≥ 18 years
- ECOG Performance Status of 0-2
- Life expectancy of at least 6 months
- Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
- Women who are pregnant or breastfeeding are ineligible for this study.
- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia: ELaboration of Treatment Approach
This is an open-labeled, single arm, Phase II, two staged study of combination of ibrutinib and rituximab in patients with autoimmune cytopenia and underlying CLL. In stage I (remission induction) patients will receive ibrutinib and rituximab for 6 months; in stage II (maintenance) - only ibrutinib until relapse, progression or unacceptable toxicity. A total of 50 patients will be enrolled into the trial. The results will be compared to historical control, efficacy of rituximab as monotherapy or in combination with chemotherapy in patients with AIC and underlying CLL.
Read the detailed description
Subjects will give informed consent before any protocol specific assessments. Blood samples, physical examination, CT scan and bone marrow examination will be performed to determine baseline disease status and study eligibility. All examinations must be performed ≤ 14 days prior to first infusion, with the exception of the CT scan and bone marrow examination. The CT scan and the bone marrow examination will be performed within 6 weeks of first infusion.
treatment regimen: Rituximab 375 mg/m2 8 weekly infusions (days 1, 8, 15, 22, 29, 36, 43, 50, 57), then 3 infusion every 28 days (days 85, 113, 141) Ibrutinib 420 mg (3 tablets) daily, constantly for 6 months
Disease status assessments to determine subject response or progression will be performed monthly according to NCI Criteria and will include:
- Physical examination including lymph node examination, spleen and liver measurement, and detection of constitutional symptoms
- Peripheral blood sample evaluation of complete blood count (CBC) and differential (expressed in % and absolutes)
- Direct antiglobulin test
- In addition, subjects will be monitored for safety, efficacy.
After completion of the induction phase, subjects achieving CR or PR (for AIC and CLL) will continue maintenance phase. During maintenance phase patients will receive:
ibrutinib 420 mg (3 tablets) daily, constantly until progression or unacceptable toxicity Survival and disease status assessments will be performed 1 month post treatment and every 2 months until total observation time.
In addition, subjects will be monitored for safety and efficacy.
- Bone marrow examination is required for confirmation of CR 1 months post final rituximab infusion. Minimal Residual Disease (MRD) assessment of the bone marrow aspirate will also be performed for subjects demonstrating a CR.
- In PRCA patients with clinical evidence of response for anemia the bone marrow examination is required independently of CLL status at 1 month post last rituximab infusion.
- All subjects with clinical CR will receive MRD assessment of the peripheral blood during maintenance phase. In subjects achieved MRD-negative result in blood in two consecutive measurements bone marrow examination is required for confirmation of CR.
- CT-Scans will be performed for patients achieving a CR, PR or SD at 1 month post last rituximab infusion. CT-Scans must be repeated every 12 months beginning since final assessment of response after induction phase.
Follow-up assessment for subjects experiencing CLL progression or relapse of AIC during the maintenance phase requires a 1 month post-treatment safety assessment. Subsequent follow up visits include assessment of survival status, date of next CLL therapy, type of therapy and response to therapy.
- Conditions
- AIHA - Warm Autoimmune Hemolytic Anemia
- Being tested
- Ibrutinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
Ibrutinib and rituximab combination for the treatment of steroid refractory AIC (warm type AIHA and PRCA) with underlying CLL.
| Study group | Role | What they receive |
|---|---|---|
| patients with AIHA and CLL | Experimental | patients with CLL and in Steroid Refractory AIHA receive ibrutinib 420 mg per day till progression or intolerance Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
Response rate defined by transfusion independence, hemoglobin level, DAT and duration of response of autoimmunity (DR-AI), defined as the interval between time point of best response and relapse of AIC. Relapses of CLL will be censored.
Measured: 3 month after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start21 Feb 2017
- Primary completion1 Dec 2019
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AIHA - Warm Autoimmune Hemolytic AnemiaStudies of the same condition, open and under way.
- 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
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eugene Nikitin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Eugene Nikitin, Association of Oncological Hematologists
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03827603
- Sponsor's protocol ID
- 54179060CLL2013
- Acronym
- ISRAEL
- Status last verified
- Jan 2020
- First submitted
- 24 Jan 2019
- Last updated
- 10 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia: ELaboration of Treatment Approach
- ClinicalTrials.gov ID
- NCT03827603
- Acronym / sponsor ID
- ISRAEL / 54179060CLL2013
- Conditions
- AIHA - Warm Autoimmune Hemolytic Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Eugene NikitinUniversity, hospital or other
- Study start
- 21 Feb 2017 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-labeled, single arm, Phase II, two staged study of combination of ibrutinib and rituximab in patients with autoimmune cytopenia and underlying CLL. In stage I (remission induction) patients will receive ibrutinib and rituximab for 6 months; in stage II (maintenance) - only ibrutinib until relapse, progression or unacceptable toxicity. A total of 50 patients will be enrolled into the trial. The results will be compared to historical control, efficacy of rituximab as monotherapy or in combination with chemotherapy in patients with AIC and underlying CLL.
Detailed description
Subjects will give informed consent before any protocol specific assessments. Blood samples, physical examination, CT scan and bone marrow examination will be performed to determine baseline disease status and study eligibility. All examinations must be performed ≤ 14 days prior to first infusion, with the exception of the CT scan and bone marrow examination. The CT scan and the bone marrow examination will be performed within 6 weeks of first infusion.
treatment regimen: Rituximab 375 mg/m2 8 weekly infusions (days 1, 8, 15, 22, 29, 36, 43, 50, 57), then 3 infusion every 28 days (days 85, 113, 141) Ibrutinib 420 mg (3 tablets) daily, constantly for 6 months
Disease status assessments to determine subject response or progression will be performed monthly according to NCI Criteria and will include:
- Physical examination including lymph node examination, spleen and liver measurement, and detection of constitutional symptoms
- Peripheral blood sample evaluation of complete blood count (CBC) and differential (expressed in % and absolutes)
- Direct antiglobulin test
- In addition, subjects will be monitored for safety, efficacy.
After completion of the induction phase, subjects achieving CR or PR (for AIC and CLL) will continue maintenance phase. During maintenance phase patients will receive:
ibrutinib 420 mg (3 tablets) daily, constantly until progression or unacceptable toxicity Survival and disease status assessments will be performed 1 month post treatment and every 2 months until total observation time.
In addition, subjects will be monitored for safety and efficacy.
- Bone marrow examination is required for confirmation of CR 1 months post final rituximab infusion. Minimal Residual Disease (MRD) assessment of the bone marrow aspirate will also be performed for subjects demonstrating a CR.
- In PRCA patients with clinical evidence of response for anemia the bone marrow examination is required independently of CLL status at 1 month post last rituximab infusion.
- All subjects with clinical CR will receive MRD assessment of the peripheral blood during maintenance phase. In subjects achieved MRD-negative result in blood in two consecutive measurements bone marrow examination is required for confirmation of CR.
- CT-Scans will be performed for patients achieving a CR, PR or SD at 1 month post last rituximab infusion. CT-Scans must be repeated every 12 months beginning since final assessment of response after induction phase.
Follow-up assessment for subjects experiencing CLL progression or relapse of AIC during the maintenance phase requires a 1 month post-treatment safety assessment. Subsequent follow up visits include assessment of survival status, date of next CLL therapy, type of therapy and response to therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients with AIHA and CLL | Experimental | Drug: Ibrutinibpatients with CLL and in Steroid Refractory AIHA receive ibrutinib 420 mg per day till progression or intolerance |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to Visit 2
- Proven diagnosis autoimmune hemolytic anemia or pure red cell aplasia
- Relapse of AIHA/PRCA after steroids, splenectomy or rituximab or refractoriness to glucocorticosteroid hormones
- No more than 2 lines of antileukemia treatment
- Hematology values must be within the following limits:
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| IbrutinibAlso: ImbruvicaIbrutinib and rituximab combination for the treatment of steroid refractory AIC (warm type AIHA and PRCA) with underlying CLL. | Drug | patients with AIHA and CLL |
Primary outcome
Response rate
Time frame: 3 month after treatment
Response rate defined by transfusion independence, hemoglobin level, DAT and duration of response of autoimmunity (DR-AI), defined as the interval between time point of best response and relapse of AIC. Relapses of CLL will be censored.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Ibrutinib in people with AIHA - Warm Autoimmune Hemolytic Anemia, run by Eugene Nikitin at 1 site in Russia.
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 17 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 10 Jan 2020. 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 Russia. 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?
Results are not available in the source record.
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 rate (time frame: 3 month after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jan 2020.