Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia (ISRAEL)
Primary Purpose
AIHA - Warm Autoimmune Hemolytic Anemia
Status
Unknown status
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
Ibrutinib
Sponsored by
About this trial
This is an interventional treatment trial for AIHA - Warm Autoimmune Hemolytic Anemia
Eligibility Criteria
Inclusion Criteria
- 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
- 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.
Sites / Locations
- Eugene Nikitin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
patients with AIHA and CLL
Arm Description
patients with CLL and in Steroid Refractory AIHA receive ibrutinib 420 mg per day till progression or intolerance
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03827603
Brief Title
Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia
Acronym
ISRAEL
Official Title
Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia: ELaboration of Treatment Approach
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 21, 2017 (Actual)
Primary Completion Date
December 1, 2019 (Actual)
Study Completion Date
March 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eugene Nikitin
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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, 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AIHA - Warm Autoimmune Hemolytic Anemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
patients with AIHA and CLL
Arm Type
Experimental
Arm Description
patients with CLL and in Steroid Refractory AIHA receive ibrutinib 420 mg per day till progression or intolerance
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
Imbruvica
Intervention Description
Ibrutinib and rituximab combination for the treatment of steroid refractory AIC (warm type AIHA and PRCA) with underlying CLL.
Primary Outcome Measure Information:
Title
Response rate
Description
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.
Time Frame
3 month after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
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
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.
Facility Information:
Facility Name
Eugene Nikitin
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
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Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia
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