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CCI-779 in B-Cell Lymphoma and Chronic Lymphocytic Leukemia (CLL)
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00290472
  Purpose

Primary Objective:

  • To determine the complete and partial response rate to CCI-779 in patients with recurrent or refractory B-cell lymphoma and CLL.

Secondary Objectives:

  • To determine the toxicity and safety of CCI-779 in patients with recurrent or refractory B-cell lymphoma and CLL.
  • To determine the relationship between the degree of activation of P13/AKT/mTOR pathway, levels of CDK inhibitors in lymphoma and response to CCI -779.
  • To determine the relationship between CCI-779 induced inactivation of mTOR and response.

Condition Intervention Phase
Lymphoma
Leukemia
Drug: CCI-779
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: CCI 779
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase II Study of CCI-779 in B-Cell Lymphoma and Chronic Lymphocytic Leukemia (CLL)

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • To learn if CCI-779 can shrink or slow the growth of B-cell lymphoma or chronic lymphocytic leukemia (CLL). [ Time Frame: 4 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study the safety of CCI-779. [ Time Frame: 4 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 101
Study Start Date: May 2005
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
CCI-779
Drug: CCI-779
25 mg IV Over 30 Minutes

Detailed Description:

CCI-779 is an experimental drug that is designed to interfere with a protein (mTOR) in the cell that plays a part in cell growth and survival. By interfering with this protein, cancer cells may stop growing or die.

Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will be asked questions about your medical history and have a physical exam. You will have your vital signs, weight, and height measured. You will have around 3 tablespoons of blood drawn for routine blood tests. You must have a negative blood pregnancy test (about 1 teaspoon) if you are a woman who is able to have children. You will have a CT (computed tomography) or a MRI (magnetic resonance imaging) scan to check on the size and locations of the cancer. You will also have a sample of bone marrow collected. To collect a bone marrow sample , an area of the hip is numbed with anesthetic and a small amount of bone marrow is withdrawn with a large needle.

If you are found to be eligible to take part in this study, you will receive the drug CCI-779 through a small needle in the vein over about 30 minutes once a week. You will receive a dose of diphenhydramine (Benadryl) by vein about 30 minutes before each dose of CCI-779 to decrease the risk of an allergic reaction to CCI-779. You will not be admitted to the hospital to receive treatment on this study.

During treatment, you will have blood draws (between 2-3 tablespoons) every week for routine tests. Every 4 weeks during treatment, you will be asked questions about your medical history and have a physical exam to check for any side effects. Every 8 weeks, you will have CT or MRI scans to see if your tumor is responding.

You will be taken off study if the disease progresses or intolerable side effects occur.

If you are taken off study for any reason, you will be asked to come back to the clinic for follow-up visits every 8 weeks. These visits will include a physical exam, routine blood tests (about 5-8 teaspoons), and CT scans.

This is an investigational study. CCI-779 is authorized for use in research only. A total of up to 101 patients will take part in this multicenter study. Between 20-40 to will be enrolled at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed recurrent or refractory B-cell lymphoma. Patients will be stratified into 3 categories: 1) aggressive B-cell lymphoma (diffuse large B-cell lymphoma and transformed lymphoma), 2) Follicular lymphoma, 3) Small lymphocytic lymphoma (including CLL and other B-cell small lymphocytic disorders, but excluding mantle cell lymphoma).
  • Measurable disease - defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as >/= 20mm w/ conventional techniques or as >/= 10mm w/ spiral CT scan. For CLL & Waldenstrom's only bone marrow involvement or peripheral blood involvement are required.
  • All Patients will have relapsed or refractory disease. Maximum number of prior therapies: Group A: (1) Patients with refractory disease (i.e. less than a partial response ot the last treatment regimen before enrollment) will have received a maximum of 3 prior treatments regimens. (2) Patients with sensitive disease (i.e. at least a partial response to the last treatment regimen before enrollment) will have received maximum of 4 prior regimens. Group B and Group C: Patients will not have received more than 5 lines of prior therapy.
  • Age >/= 18 years
  • Life expectancy > 3 months
  • ECOG performance status </= 2
  • Normal organ and acceptable marrow function: (1) ANC >/= 1,000/microL; (2) PLT >/= 50,000/microL*; (3) Bilirubin l</= 1.5 institutional ULN**; (4) AST/ALT </= 2.5 X ULN; (5) creatinine </= 1.5 ULN; (6) fasting serum cholesterol </= 350 mg/dL; (7) fasting triglycerides </= 400mg/dL (* patients with thrombocytopenia due to bone marrow involvement must has platelets > 20,000/microL. NOTE: Patients with elevated unconjugated bilirubin due to Gilbert's disease will be eligible.)
  • Must agree to use adequate contraception prior to study entry and for the duration of participation
  • Ability to understand and willingness to sign a written informed consent document
  • Presence of peripheral lymph node involvement, bone marrow involvement or blood involvement is required. In the case of bone marrow involvement, there should be at least 10% bone marrow involvement as evaluated by an appropriate core biopsy.
  • Patients will have exhausted all potentially curative treatment options because of lack of response, relapse, or ineligibility.
  • Caveats: (1) Patients who have failed autologous transplant are eligible. The salvage regimen given before autologous transplantation, the conditioning regimen and any maintenance given after transplantation will be counted as one treatment regimen. (2) Prior treatment with rituximab or campath will not be considered prior therapy as these treatments are often repeatedly administered and are devoid of serious myelosuppressive effects. (3) There is no limitation to the amount of prior radiotherapy received.

Exclusion Criteria:

  • Patients with mantle cell lymphoma
  • Chemotherapy or radiation therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving other investigational agents
  • Patients with known CNS involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779
  • No unconventional therapies, food, or vitamin supplements containing St. John's Wort are allowed. (St. John's Wort is a known inducer of the CYP3A4 and therefore potentially interfering with the metabolism of CCI-779).
  • Patients with currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because CCI-779 is an inhibitor of mRNA translation with the potential for teratogens or abortifacient effects. Because there is an unknown risk for adverse events in nursing infants secondary to treatment of the mother with CCI-779, breast feeding should be discouraged if the mother is treated with CCI-779.
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with CCI-779. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00290472

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Barbara Pro, MD The University of Texas MD Anderson Cancer Center
  More Information

UT MD Anderson Cancer Center  This link exits the ClinicalTrials.gov site

Responsible Party: U.T.M.D. Anderson Cancer Center ( Barbara Pro, MD/Associate Professor )
Study ID Numbers: 2004-0612
Study First Received: February 10, 2006
Last Updated: October 30, 2008
ClinicalTrials.gov Identifier: NCT00290472  
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Lymphoma
Leukemia
CCI-779
Temsirolimus
Torisel

Study placed in the following topic categories:
Chronic lymphocytic leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Leukemia, B-cell, chronic
Lymphoma, B-Cell
Leukemia
Lymphatic Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
B-cell lymphomas
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009