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Phase II Trial of Perifosine in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Phase 2
18 Years
Not Enrolling
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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Trial Information

Phase II Trial of Perifosine in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia and small B-cell lymphocytic lymphoma represent different
manifestations of the same disease. CLL/SLL (hereafter denoted by CLL) is a clonal disorder
of small B lymphocytes expressing a characteristic morphology and immunophenotype. The B
cells express CD19, dim CD 20, dim CD 5, CD 23, CD 43, CD 79a, and weakly express surface
immunoglobin. CLL can present asymptomatically in 25% of patients when diagnosed on a
complete blood count. It also can present with diffuse painless lymphadenopathy and, in a
smaller number of patients, B symptoms.

CLL is characterized by accumulation of circulating B cells predominantly in the G0 phase of
the cell cycle. These cells are resistant to apoptosis. CLL has been found to have aberrant
signaling in several pathways including NF-kB, Akt/PI3K, and JNK/STAT pathways. Akt is
important in promoting CLL survival and viability, as seen in in vitro experiments where
blocking its activity results in apoptosis. Thus an AKT inhibitor may lead to increased
apoptosis and may have a role in the treatment of this disease.

Treatment options for CLL range from a watch and wait approach to high dose chemotherapy
with stem cell support. Currently, there is no consensus on the best treatment regimen,
since no treatment has been shown to improve survival in randomized prospective clinical
trials. New approaches to treatment, especially those with lower toxicity rates, are needed.

Perifosine has been shown to inhibit or otherwise modify signaling through a number of
different signal transduction pathways, including Akt, MAPK, and JNK. These pathways are
involved in the development of cancers and resistance to chemotherapy. Perifosine is of
particular interest, especially due to the difficulty in discovery of drugs that inhibit
these pathways with minimal toxicity. The effect of perifosine on CLL cells has been tested
in the laboratory and has been shown to be an active agent against primary CLL cells in

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response

Outcome Description:

Per International Workshop on Chronic Lymphocytic Leukemia, Complete Response (CR):normal CBC; absence of the following: clonal lymphocytes in blood and marrow, lymphadenopathy, hepatomegaly or splenomegaly, and constitutional symptoms; and bone marrow has <30% lymphocytes, is normocellular, and is without B-lymphoid nodules. Partial Response(PR): one of the following: decrease lymphadenopathy ≥ 50%; decrease of liver and/or spleen size ≥ 50%, any constitutional symptoms, Polymorphonuclear leukocytes ≥ 1,500/µl or a 50% improvement, or decrease of circulating clonal B lymphocytes ≥ 50% AND one of the following: Platelets ≥ 100,000/µl or a 50% improvement, Hemoglobin ≥ 11.0 g/dl or a 50% improvement, Bone marrow has ≥ 30% lymphocytes, or B-lymphoid nodules, or not done. Overall Response (OR)= CR+PR

Outcome Time Frame:

after 3 months of treatment

Safety Issue:


Principal Investigator

Daphne Friedman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

April 2013

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • B-Cell Chronic Lymphocytic Leukemia
  • Leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma



Duke University Medical Center Durham, North Carolina  27710