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Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter's Transformation

Primary Purpose

Prolymphocytic Leukemia, Recurrent Mantle Cell Lymphoma, Recurrent Small Lymphocytic Lymphoma

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
sotrastaurin acetate
pharmacological study
laboratory biomarker analysis
Sponsored by
James Blachly
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prolymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy >= 2 months
  • Appropriate histologic diagnosis (a) or (b):

    • (a) Histologically documented diagnosis of intermediate or high risk CLL/SLL, B-PLL, and RT arising from CLL/SLL according to the 2008 guidelines, meeting criteria for active disease requiring treatment:

      • Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
      • Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
      • Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
      • Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
      • Constitutional symptoms including any of the following:

        • Unintentional weight loss of 10% or more within 6 mos.
        • Significant fatigue limiting activity
        • Fevers >= 100.5 degrees F for 2 weeks or more without evidence of infection
        • Night sweats > 1 month without evidence of infection
      • Need for cytoreduction prior to stem cell transplantation
    • (b) Pathologically documented MCL [defined as either t(11;14) or overexpression of cyclin D1] for the MCL pilot study
  • Relapsed after or refractory to at least one prior therapy
  • Willingness to undergo all study-related evaluations and procedures
  • Ability to understand and willingness to execute a written informed consent document

Exclusion Criteria:

  • Prior therapy as follows:

    • Major surgery within 2 weeks
    • Corticosteroids greater than 20 mg/day prednisone (or equivalent) within 2 weeks unless used by inhalation or topical route, or unless necessary for premedication before iodinated contrast dye, or for autoimmune hemolytic anemia
    • Cytotoxic chemotherapy or biologic therapy within 4 weeks, excepting BCR kinase inhibitors for which no wash out is required, or
    • Nitrosoureas within the 6 weeks of the planned first dose of the study drug
  • Failure to recover toxicity from prior chemo- or radiotherapy to grade 1
  • Known active leukemia or lymphoma of the central nervous system (CNS) requiring therapy
  • Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: absolute neutrophil count (ANC) < 1 x 10^9/L
  • Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: platelets < 30 x 10^9/L
  • Serum total bilirubin > 2 x ULN (upper limit of normal)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN, or > 5 x ULN if CLL/lymphoma is present in the liver
  • Estimated glomerular filtration rate (GFR) < 30 mL/min
  • Patients who are receiving treatment with medications that are known to be strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and CYP3A4/5 substrates with QT prolongation risk that cannot be discontinued prior to study entry
  • Clinically significant cardiac diseases, including any of the following:

    • History or presence of ventricular tachyarrhythmia
    • Presence of unstable/uncontrolled atrial fibrillation (with ventricular rate > 100 beats per minute [bpm]); patients with stable atrial fibrillation are eligible provided that they do not meet any of the other exclusion criteria
    • Angina pectoris or acute myocardial infarction within 3 months of starting study drug
    • New York Heart Association (NYHA) functional class III or IV heart failure
    • Labile or uncontrolled hypertension
  • History of another malignancy that limits survival to less than 2 years in the estimate of the investigator; basal and squamous cell cancers of the skin, or squamous cell carcinoma of the cervix in situ, which were completely resected or otherwise cured, or localized prostate cancer (Gleason < 5) are eligible
  • Gastrointestinal dysfunction, including motility or malabsorption syndromes or inflammatory bowel disease which could limit absorption of AEB071
  • Known human immunodeficiency virus (HIV) positivity, or active hepatitis B or C infection with detectible viral nucleic acid in the blood; testing for these viruses is not a required part of screening
  • Severe systemic infections requiring intravenous antibiotics within the two weeks prior to initiation of AEB071
  • Lactating or pregnant
  • Women of child-bearing potential or male partners of women of child-bearing potential who will not agree to use highly effective method of contraception throughout the entire study period and for a minimum of 5 terminal half-lives of AEB071 (approximately 36 hours) after the last dose of study drug; highly effective contraception methods include:

    • Total abstinence or
    • Male or female sterilization or
    • Combination of any two of the following (a+b or a+c or b+c):

      • a. Use of oral, injected or implanted hormonal methods of contraception
      • b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
      • c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential
  • Any other life-threatening illness or medical condition that, in the opinion of the investigator, could compromise the safety of the patient or interfere with analysis of study endpoints

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment (sotrastaurin acetate)

    Arm Description

    Patients receive sotrastaurin acetate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Outcomes

    Primary Outcome Measures

    Proportion of CLL/SLL/PLL/RT patients who achieve an objective clinical response, estimated by the number of complete, partial, or partial responses with lymphocytosis divided by the total number of evaluable patients
    Categories of response for CLL and PLL patients defined according to criteria published by the International Workshop on CLL. Response for SLL/RT patients will be according to revised response criteria for malignant lymphoma. The objective response rate for all evaluable patients in the phase II study will be calculated with an exact 95% binomial confidence interval (assuming that the number of patients who respond is binomially distributed).

    Secondary Outcome Measures

    Response duration
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Progression free survival (PFS)
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Overall survival (OS)
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Rate of objective clinical response (CR, PR) (optional PLCG2 enriched cohort, if activated)
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Response duration (optional PLCG2 enriched cohort, if activated)
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    PFS (optional PLCG2 enriched cohort, if activated)
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    OS (optional PLCG2 enriched cohort, if activated)
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Rate of objective clinical response (CR, PR) (MCL cohort)
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Response duration (MCL cohort)
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    PFS (MCL cohort)
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    OS (MCL cohort)
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Incidence of adverse events (AEs), assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria
    For each disease group, frequency and severity of adverse events will be collected and summarized by descriptive statistics.
    Frequency of AEs requiring dose reduction or drug discontinuation
    Number of patients who require dose modifications and/or dose delays will be assessed.
    Number of courses completed
    Number of courses started/completed and the reasons for going off-treatment will be assessed.
    Pharmacodynamic modulation of the downstream targets of the BCR (including LCP1) after sotrastaurin acetate treatment
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships. Changes in BCR signaling over time may be evaluated quantitatively using repeated measures models and graphically with individual time plots or box plots.
    Pharmacodynamic modulation of the downstream targets of nuclear transcription factor kappa-B after sotrastaurin acetate treatment
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships.
    Pharmacodynamic modulation of downstream targets of WNT/beta-catenin pathway
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships.
    Genomic features associated with response by deep sequencing panel targeted at recurrent mutations in CLL
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships.

    Full Information

    First Posted
    November 4, 2014
    Last Updated
    April 3, 2017
    Sponsor
    James Blachly
    Collaborators
    Novartis
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02285244
    Brief Title
    Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter's Transformation
    Official Title
    A Phase 2 Feasibility Study of Sotrastaurin for Relapsed and Refractory CLL/SLL/PLL/RT
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2017
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Decision made by the Principal Investigator
    Study Start Date
    March 12, 2015 (Actual)
    Primary Completion Date
    March 12, 2015 (Actual)
    Study Completion Date
    March 12, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    James Blachly
    Collaborators
    Novartis

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This phase II trial studies how well sotrastaurin acetate works in treating patients with chronic lymphocytic leukemia, small lymphocytic leukemia, prolymphocytic leukemia, or Richter's transformation that has returned or that does not respond to treatment. Sotrastaurin acetate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
    Detailed Description
    PRIMARY OBJECTIVES: I. To determine the objective clinical response rate of AEB071 (sotrastaurin acetate) treatment in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL)/Richter's transformation (RT). SECONDARY OBJECTIVES: I. To determine the feasibility and tolerability of long-term administration of a fixed dose of AEB071 in patients with relapsed or refractory CLL/SLL/PLL. II. To examine select downstream pharmacodynamic effects in this population of patients after receiving AEB071 including assessment of the wingless-type MMTV integration site family (WNT) signaling pathway. III. To determine the feasibility and tolerability of AEB071 treatment in patients with relapsed or refractory mantle cell lymphoma (MCL) as well as to gain preliminary data regarding efficacy in this patient population. TERTIARY OBJECTIVES: I. Determine the proportion of patients with select germline and somatic deoxyribonucleic acid (DNA) alterations, including in the B-cell receptor (BCR) pathway. II. Determine how mutational and transcriptional status in key genes affects response to this therapy and may have affected response to prior therapies. OUTLINE: Patients receive sotrastaurin acetate orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then at least every 3 months thereafter.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Prolymphocytic Leukemia, Recurrent Mantle Cell Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Richter Syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment (sotrastaurin acetate)
    Arm Type
    Experimental
    Arm Description
    Patients receive sotrastaurin acetate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Intervention Type
    Drug
    Intervention Name(s)
    sotrastaurin acetate
    Other Intervention Name(s)
    AEB 071, AEB071
    Intervention Description
    Given PO
    Intervention Type
    Other
    Intervention Name(s)
    pharmacological study
    Other Intervention Name(s)
    pharmacological studies
    Intervention Description
    Correlative studies
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    Correlative studies
    Primary Outcome Measure Information:
    Title
    Proportion of CLL/SLL/PLL/RT patients who achieve an objective clinical response, estimated by the number of complete, partial, or partial responses with lymphocytosis divided by the total number of evaluable patients
    Description
    Categories of response for CLL and PLL patients defined according to criteria published by the International Workshop on CLL. Response for SLL/RT patients will be according to revised response criteria for malignant lymphoma. The objective response rate for all evaluable patients in the phase II study will be calculated with an exact 95% binomial confidence interval (assuming that the number of patients who respond is binomially distributed).
    Time Frame
    Up to 9 months
    Secondary Outcome Measure Information:
    Title
    Response duration
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years
    Title
    Progression free survival (PFS)
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years
    Title
    Overall survival (OS)
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from the first dose of the study drug until death, assessed up to 3 years
    Title
    Rate of objective clinical response (CR, PR) (optional PLCG2 enriched cohort, if activated)
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Up to 3 years
    Title
    Response duration (optional PLCG2 enriched cohort, if activated)
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years
    Title
    PFS (optional PLCG2 enriched cohort, if activated)
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years
    Title
    OS (optional PLCG2 enriched cohort, if activated)
    Description
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from the first dose of the study drug until death, assessed up to 3 years
    Title
    Rate of objective clinical response (CR, PR) (MCL cohort)
    Description
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Up to 3 years
    Title
    Response duration (MCL cohort)
    Description
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years
    Title
    PFS (MCL cohort)
    Description
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years
    Title
    OS (MCL cohort)
    Description
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from the first dose of the study drug until death, assessed up to 3 years
    Title
    Incidence of adverse events (AEs), assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria
    Description
    For each disease group, frequency and severity of adverse events will be collected and summarized by descriptive statistics.
    Time Frame
    Up to 30 days post-treatment
    Title
    Frequency of AEs requiring dose reduction or drug discontinuation
    Description
    Number of patients who require dose modifications and/or dose delays will be assessed.
    Time Frame
    Up to 30 days post-treatment
    Title
    Number of courses completed
    Description
    Number of courses started/completed and the reasons for going off-treatment will be assessed.
    Time Frame
    Up to 30 days post-treatment
    Title
    Pharmacodynamic modulation of the downstream targets of the BCR (including LCP1) after sotrastaurin acetate treatment
    Description
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships. Changes in BCR signaling over time may be evaluated quantitatively using repeated measures models and graphically with individual time plots or box plots.
    Time Frame
    Baseline to up to course 1 day 29
    Title
    Pharmacodynamic modulation of the downstream targets of nuclear transcription factor kappa-B after sotrastaurin acetate treatment
    Description
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships.
    Time Frame
    Baseline to up to course 1 day 29
    Title
    Pharmacodynamic modulation of downstream targets of WNT/beta-catenin pathway
    Description
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships.
    Time Frame
    Baseline to up to course 1 day 29
    Title
    Genomic features associated with response by deep sequencing panel targeted at recurrent mutations in CLL
    Description
    Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group graphically to assess potential patterns and relationships.
    Time Frame
    Up to course 1 day 29

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Life expectancy >= 2 months Appropriate histologic diagnosis (a) or (b): (a) Histologically documented diagnosis of intermediate or high risk CLL/SLL, B-PLL, and RT arising from CLL/SLL according to the 2008 guidelines, meeting criteria for active disease requiring treatment: Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia) Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy Constitutional symptoms including any of the following: Unintentional weight loss of 10% or more within 6 mos. Significant fatigue limiting activity Fevers >= 100.5 degrees F for 2 weeks or more without evidence of infection Night sweats > 1 month without evidence of infection Need for cytoreduction prior to stem cell transplantation (b) Pathologically documented MCL [defined as either t(11;14) or overexpression of cyclin D1] for the MCL pilot study Relapsed after or refractory to at least one prior therapy Willingness to undergo all study-related evaluations and procedures Ability to understand and willingness to execute a written informed consent document Exclusion Criteria: Prior therapy as follows: Major surgery within 2 weeks Corticosteroids greater than 20 mg/day prednisone (or equivalent) within 2 weeks unless used by inhalation or topical route, or unless necessary for premedication before iodinated contrast dye, or for autoimmune hemolytic anemia Cytotoxic chemotherapy or biologic therapy within 4 weeks, excepting BCR kinase inhibitors for which no wash out is required, or Nitrosoureas within the 6 weeks of the planned first dose of the study drug Failure to recover toxicity from prior chemo- or radiotherapy to grade 1 Known active leukemia or lymphoma of the central nervous system (CNS) requiring therapy Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: absolute neutrophil count (ANC) < 1 x 10^9/L Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: platelets < 30 x 10^9/L Serum total bilirubin > 2 x ULN (upper limit of normal) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN, or > 5 x ULN if CLL/lymphoma is present in the liver Estimated glomerular filtration rate (GFR) < 30 mL/min Patients who are receiving treatment with medications that are known to be strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and CYP3A4/5 substrates with QT prolongation risk that cannot be discontinued prior to study entry Clinically significant cardiac diseases, including any of the following: History or presence of ventricular tachyarrhythmia Presence of unstable/uncontrolled atrial fibrillation (with ventricular rate > 100 beats per minute [bpm]); patients with stable atrial fibrillation are eligible provided that they do not meet any of the other exclusion criteria Angina pectoris or acute myocardial infarction within 3 months of starting study drug New York Heart Association (NYHA) functional class III or IV heart failure Labile or uncontrolled hypertension History of another malignancy that limits survival to less than 2 years in the estimate of the investigator; basal and squamous cell cancers of the skin, or squamous cell carcinoma of the cervix in situ, which were completely resected or otherwise cured, or localized prostate cancer (Gleason < 5) are eligible Gastrointestinal dysfunction, including motility or malabsorption syndromes or inflammatory bowel disease which could limit absorption of AEB071 Known human immunodeficiency virus (HIV) positivity, or active hepatitis B or C infection with detectible viral nucleic acid in the blood; testing for these viruses is not a required part of screening Severe systemic infections requiring intravenous antibiotics within the two weeks prior to initiation of AEB071 Lactating or pregnant Women of child-bearing potential or male partners of women of child-bearing potential who will not agree to use highly effective method of contraception throughout the entire study period and for a minimum of 5 terminal half-lives of AEB071 (approximately 36 hours) after the last dose of study drug; highly effective contraception methods include: Total abstinence or Male or female sterilization or Combination of any two of the following (a+b or a+c or b+c): a. Use of oral, injected or implanted hormonal methods of contraception b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential Any other life-threatening illness or medical condition that, in the opinion of the investigator, could compromise the safety of the patient or interfere with analysis of study endpoints
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    James Blachly, MD
    Organizational Affiliation
    The Ohio State University Wexner Medical Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://cancer.osu.edu
    Description
    The Jamesline

    Learn more about this trial

    Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter's Transformation

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