Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia (ISRAEL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03827603
Recruitment Status : Active, not recruiting
First Posted : February 1, 2019
Last Update Posted : January 10, 2020
Information provided by (Responsible Party):
Eugene Nikitin, Association of Oncological Hematologists

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.

Condition or disease Intervention/treatment Phase
AIHA - Warm Autoimmune Hemolytic Anemia Drug: Ibrutinib Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ibrutinib in Steroid Refractory Autoimmune Hemolytic Anemia: ELaboration of Treatment Approach
Actual Study Start Date : February 21, 2017
Actual Primary Completion Date : December 1, 2019
Estimated Study Completion Date : March 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: patients with AIHA and CLL
patients with CLL and in Steroid Refractory AIHA receive ibrutinib 420 mg per day till progression or intolerance
Drug: Ibrutinib
Ibrutinib and rituximab combination for the treatment of steroid refractory AIC (warm type AIHA and PRCA) with underlying CLL.
Other Name: Imbruvica

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  1. Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to Visit 2
  2. Proven diagnosis autoimmune hemolytic anemia or pure red cell aplasia
  3. Relapse of AIHA/PRCA after steroids, splenectomy or rituximab or refractoriness to glucocorticosteroid hormones
  4. No more than 2 lines of antileukemia treatment
  5. Hematology values must be within the following limits:

    1. Absolute neutrophil count 1000/mm3 independent of growth factor support
    2. Platelets 100.000/mm3 or 50.000/mm3 if bone marrow involvement independent of transfusion support in either situation
  6. Biochemical values within the following limits:

    1. Alanine aminotransferase and aspartate aminotransferase less 3 upper limit of normal (ULN)
    2. Total bilirubin less 1.5x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
    3. Serum creatinine less 2 x ULN or estimated Glomerular Filtration Rate more 40 mL/min/1.73 m2
  7. Age ≥ 18 years
  8. ECOG Performance Status of 0-2
  9. Life expectancy of at least 6 months
  10. 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.
  11. Women who are pregnant or breastfeeding are ineligible for this study.
  12. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03827603

Layout table for location information
Russian Federation
Eugene Nikitin
Moscow, Russian Federation, 125284
Sponsors and Collaborators
Eugene Nikitin

Layout table for additonal information
Responsible Party: Eugene Nikitin, Professor, Association of Oncological Hematologists Identifier: NCT03827603    
Other Study ID Numbers: 54179060CLL2013
First Posted: February 1, 2019    Key Record Dates
Last Update Posted: January 10, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases