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

NCT00873457 | Completed Phase 2 Results

• 1 other identifier: Pro00015060
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

B-Cell Chronic Lymphocytic Leukemia; Leukemia

Outcome Measures

Primary Outcomes (2)

• Overall Response

  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

  after 3 months of treatment

• Overall Response

  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

  after 6 months of treatment

Secondary Outcomes (2)

• Overall Survival

  up to a maximum of 2 years

• Event-free Survival

  up to a maximum of 2 years

Study Arms (1)

Perifosine

EXPERIMENTAL

Perifosine 50 mg twice a day for a total of six 28-day cycles.

Drug: perifosine

Interventions

perifosine DRUG

Perifosine 50 mg will be taken orally twice a day for a maximum of six 28-day cycles

Also known as: D-21266

Perifosine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Daphne Friedman: lead
• Keryx Biopharmaceuticals: collaborator
• Keryx / AOI Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia

Interventions

perifosine

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed. All patients were heavily pretreated and had aggressive disease.

Results Point of Contact

• Title: Daphne Friedman, MD
• Organization: Duke University Medical Center

daphne.friedman@dm.duke.edu

919-684-9220

Study Officials

• Daphne Friedman, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Instructor, Medicine - Hematological Malignancies

Study Record Dates

• First Submitted: March 30, 2009
• First Posted: April 1, 2009
• Study Start: August 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: April 1, 2013
• Last Updated: May 27, 2013
• Results First Posted: January 24, 2013

Record last verified: 2013-05

Locations

US (1)