Perifosine in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: perifosine
Intervention description: Perifosine 50 mg will be taken orally twice a day for a maximum of six 28-day cycles
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: B-Cell Chronic Lymphocytic Leukemia; Leukemia

Summary:

      Perifosine inhibits the AKT pathway (a way cells communicate with each other). This pathway
      is felt to be important in the development of several types of cancers including chronic
      lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It is thought perifosine may
      be able to block this pathway and lead to an improvement in the CLL or SLL. The purpose of
      this trial is to see if perifosine is an effective treatment for relapsed or refractory CLL
      or SLL. Another purpose of this study is to look at the effect perifosine has on cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A diagnosis of CLL or SLL based on iwCLL diagnostic criteria.

          -  Prior therapy for CLL (no limit on number of prior regimens).

          -  Patients requiring therapy, based on at least one of the iwCLL criteria.

          -  18 years of age or older.

          -  Performance status ECOG 0, 1, or 2.

          -  An estimated or measured creatinine clearance ≥30 ml/min at study enrollment.

          -  AST, ALT, and total bilirubin ≤ 2.5 times the upper limit of normal, unless due to
             CLL/SLL.

          -  Female subject who is either post-menopausal or surgically sterilized or male or
             female subject willing to use an acceptable method of birth control for the duration
             of the study therapy and for 2 weeks after study therapy completion.

        Exclusion Criteria:

          -  Female subject is pregnant or lactating.

          -  Patient has received other investigational drugs for this disease within 14 days of
             enrollment.

          -  Patient with known HIV prior to enrollment.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Patients with another malignancy within the last three years (from documentation of
             remission) other than basal or squamous cell skin cancer or CIS of the cervix or early
             stage prostate cancer not requiring systemic treatment.

          -  Patients who underwent allogeneic stem cell transplant and have at least 2% donor
             cells engrafted will be excluded.

          -  Significant cardiac or vascular events within 6 months: acute MI, unstable angina,
             severe peripheral vascular disease (ischemic pain at rest class 3 or worse,
             non-healing ulcers/wounds, congestive heart failure (NHYA class ≥ 2), uncontrolled
             cardiac arrhythmias.

          -  Known severe hypersensitivity to perifosine or any component of the formulation.

          -  Life expectancy less than six months due to co-morbid illness

          -  Active autoimmune hemolytic anemia or immune thrombocytopenia, requiring current
             steroid therapy.

          -  De novo prolymphocytic leukemia (PLL) or PLL arising from CLL (≥ 55% prolymphocytes).

          -  Richter's transformation