Perifosine in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

This study has been completed.
Sponsor:
Collaborators:
Keryx Biopharmaceuticals
Keryx / AOI Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Daphne Friedman, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00873457
First received: March 30, 2009
Last updated: May 19, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Drug: perifosine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Perifosine in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Overall Response [ Time Frame: after 3 months of treatment ] [ Designated as safety issue: No ]
    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

  • Overall Response [ Time Frame: after 6 months of treatment ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: up to a maximum of 2 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the length of time between discontinuation of perifosine until death or 2 year's followup, whichever comes first.

  • Event-free Survival [ Time Frame: up to a maximum of 2 years ] [ Designated as safety issue: No ]
    Event-free survival will be defined as the length of time between the discontinuation of study treatment and disease progression, next therapy, or death,whichever comes first, up to a maximum of 2 years.


Enrollment: 16
Study Start Date: August 2009
Study Completion Date: April 2013
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Perifosine
Perifosine 50 mg twice a day for a total of six 28-day cycles.
Drug: perifosine
Perifosine 50 mg will be taken orally twice a day for a maximum of six 28-day cycles
Other Name: D-21266

Detailed Description:

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 vitro.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00873457

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Daphne Friedman
Keryx Biopharmaceuticals
Keryx / AOI Pharmaceuticals, Inc.
Investigators
Principal Investigator: Daphne Friedman, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Daphne Friedman, Medical Instructor, Medicine - Hematological Malignancies, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00873457     History of Changes
Other Study ID Numbers: Pro00015060
Study First Received: March 30, 2009
Results First Received: December 15, 2012
Last Updated: May 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
B-Cell Chronic Lymphocytic Leukemia
Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 28, 2014