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Clinical-biological Characteristics and Outcome of Chronic Lymphocytic Leukemia Under Ibrutinib-named Patient Program

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: NCT02582320
Recruitment Status : Completed
First Posted : October 21, 2015
Last Update Posted : October 6, 2020
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary:
This is a retrospective observational study aimed at describing the characteristics and outcome of CLL patients included in the NPP in Italy in a period of time ranging from the start of the NPP until November, 30th 2014. A longitudinal survey will be carried out by collecting data of patients who received at least 1 dose of Ibrutinib. All patients will be observed for at least 12 months from the treatment start.

Condition or disease Intervention/treatment
Chronic Lymphocytic Leukemia Drug: Ibrutinib

Detailed Description:

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The disease is characterized by the progressive accumulation of phenotypically mature malignant B lymphocytes, primarily in the peripheral blood, bone marrow, and lymph nodes. Over the last 10-15 years several biological prognostic markers have been identified, starting from the immunoglobulin gene mutational analysis to CD38, ZAP70, CD49d expression, and many others. The very recent discovery of several new genes that carry point mutations in CLL, including NOTCH1, SF3B1 and BIRC3, has added more markers that seem to correlate with resistance to treatment and with transformation into Richter syndrome. A large number of chemoimmunotherapy regimens are currently considered for the treatment of CLL patients.

NPP program The Named Patient Program (NPP) is a program intended to provide early access to ibrutinib in Italy. This program is specifically for patients who have relapsed or refractory chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma.

Rationale In patients with CLL Ibrutinib, given as single agent has shown marked activity and a good safety profile. Data from patients treated with ibrutinib outside a controlled clinical trial within a National Patient Program (NPP) could give additional information about the clinical use, treatment duration, efficacy, and toxicity of ibrutinib given to CLL patients in a real life context.

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Study Type : Observational
Actual Enrollment : 264 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: A Retrospective Study to Evaluate the Clinical-Biologic Characteristics and Outcome of Patients Treated in Italy According to the Ibrutinib-Named Patient Program for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Actual Study Start Date : March 2016
Actual Primary Completion Date : October 2018
Actual Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Group/Cohort Intervention/treatment
Study patients
Patients with Relapsed or refractory CLL or 17p deleted CLL fulfilling the eligibility criteria required by the Named Patient Program (NPP) who received at least 1 dose of Ibrutinib 420 mg daily before November, 30th 2014.
Drug: Ibrutinib
A longitudinal survey will be carried out by collecting data of patients who received at least 1 dose of Ibrutinib. All patients will be observed for at least 12 months from the treatment start.

Primary Outcome Measures :
  1. Number of patients who progress [ Time Frame: At 12 months from the start of Ibrutinib ]

Secondary Outcome Measures :
  1. Number of patients who respond to treatment [ Time Frame: At 12 months from enrolment ]
    CR,PR, L-PR according to the IWCLL 2008 criteria with modification for treatment-related lymphocytosis

  2. Treatment duration [ Time Frame: At 12 months from enrolment ]
  3. Time to next treatment in terms of number of days needed [ Time Frame: At 12 months from treatment start ]
  4. Number of patients surviving [ Time Frame: At 12 months from treatment start ]
    Overall survival

  5. Number of patients who reach normal values in the immunoglobulin levels [ Time Frame: At 3, 6 and 12 months from treatment start ]
  6. Number of patients with toxic events [ Time Frame: At 12 months from treatment start ]
  7. Number of patients who develop Richter's syndrome and secondary malignancies [ Time Frame: At 12 months from treatment start ]
  8. Number of patients who require added assistance [ Time Frame: At 12 months from treatment start ]
    For example: hospitalization, emergency visits, blood product transfusions and use of hematopoietic growth factors, antibiotics.

  9. Number of patients who fail to treatment. [ Time Frame: At 12 months from treatment start ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with R/R CLL or 17p deleted CLL fulfilling the eligibility criteria required by the NPP who received at least 1 dose of Ibrutinib 420 mg daily before November, 30th 2014

NPP Inclusion Criteria:

  1. Patients ≥18 years of age.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
  3. A minimum of one prior line of systemic chemotherapy, chemo-immunotherapy, or an alemtuzumab-based regimen, consisting of at least two cycles of therapy.
  4. Relapsed or refractory CLL with one or more of the following criteria:

    • Presence of deletion of the short-arm of chromosome 17 (ie 17p deletion).
    • Relapsed: Failed two or more previous treatments, at least one with a purine analogue such as fludarabine.
    • Relapsed: Progression-free interval of less than 24 months from completing treatment with a nucleoside analogue, or bendamustine-containing regimen in combination with an anti-CD20 monoclonal antibody such as rituximab.
    • Refractory: Failure to respond to a prior chemotherapy-based treatment, stable disease, or disease progression while on treatment.
  5. Patient has active CLL requiring treatment as defined by the IWCLL 2008 criteria. A minimum of one of the following criteria is required:

    • Evidence of progressive marrow failure, as manifested by the development of, or worsening of, anemia or thrombocytopenia.
    • Massive (at least 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.

      c. Massive nodes (at least 10 cm in longest diameter), progressive, or symptomatic lymphadenopathy.

    • Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time of less than 6 months (which may be extrapolated). For patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/mL), lymphocyte doubling time should not be used as a single parameter to define indication for treatment. Factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
    • Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs:

      i. Unintentional weight loss >10% within the previous 6 months prior to screening.

    ii. Significant fatigue (inability to work or perform usual activities). iii. Fever higher than 38.0°C for 2 or more weeks without evidence of infection.

    iv. Night sweats for more than 1 month without evidence of infection.

  6. Haematology values within the following parameters:

    • Absolute neutrophil count (ANC) of ≥0.75 x109/L independent of growth factor support.
    • Platelet count of ≥30 x109/L independent of platelet support.
  7. Biochemical values within the following limits:

    • Serum creatinine ≤2 times the upper limit of normal (ULN) or estimated glomerular filtration rate (GFR [Crockcoft-Gault]) ≥30 mL/minute.
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN.
    • Total bilirubin ≤1.5 times ULN (unless the bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) for whom the upper limit of serum bilirubin is 3 mg/dl.
  8. No problems to swallowing regularly capsules.
  9. Agreed to practice a highly effective method of birth control during and after participation in the NPP if they are of childbearing potential and sexually active.
  10. Signed informed consent document (if feasible) indicating that they understand the purpose of the study, they agree to give complete access to their medical records.

NPP Exclusion criteria

  1. Previous treatment with ibrutinib or participation to an ibrutinib clinical trial (ibrutinib or comparator arm).
  2. Eligible to participate in a currently recruiting ibrutinib clinical trial.
  3. Previously received ibrutinib as part of a clinical trial.
  4. Previously received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib.
  5. Currently enrolled in an interventional clinical trial.
  6. Currently receiving chemotherapy, anticancer immunotherapy, or experimental therapy.
  7. Currently recovering from acute toxicities of prior treatment for CLL.
  8. Received stem cell transplantation within the past 6 months.
  9. Evidence of graft-versus-host disease and/or requires immunosuppressant therapy.
  10. Major surgery within the past 4 weeks or a major wound that has not fully healed.
  11. History of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B.
  12. Ongoing uncontrolled active systemic infection.
  13. Uncontrolled autoimmune haemolytic anemia (AIHA).
  14. Uncontrolled idiopathic thrombocytopenic purpura (ITP).
  15. Central nervous system leukemia/lymphoma or Richter's transformation.
  16. Diagnosed or treated for another malignancy, other than CLL, except for:

    • Malignancy treated with curative intent and with no known active disease present for ≥3 years prior to entering this named patient program and considered to be at low risk for recurrence.
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
    • Adequately treated cervical carcinoma in situ without evidence of disease.
  17. Stroke within the past 6 months.
  18. Intracranial haemorrhage within the past 6 months.
  19. Requires anticoagulation with warfarin or equivalent vitamin K antagonist (e.g. phenprocoumon).
  20. Requires treatment with a strong CYP3A inhibitor.
  21. Clinically significant cardiovascular disease such as:

    • Uncontrolled or symptomatic arrhythmias.
    • Congestive heart failure.
    • Myocardial infarction within the past 6 months.
    • Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
  22. Patient has any life-threatening illness, medical condition, clinically significant.

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): NCT02582320

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Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
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Study Chair: Roberto Foà Policlinico Umberto I, Hematology Department.
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Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto Identifier: NCT02582320    
Other Study ID Numbers: LLC1415
First Posted: October 21, 2015    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell