CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00290472
First received: February 10, 2006
Last updated: May 7, 2014
Last verified: February 2013
  Purpose

Drugs used in chemotherapy, such as CCI-779, work in different ways to stop cancer cells from dividing so they stop growing or die. This phase II trial is studying how well CCI-779 works in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Malignant Neoplasm
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Splenic Marginal Zone Lymphoma
Waldenström Macroglobulinemia
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of CCI-779 in B-cell Lymphoma and CLL

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective Overall Response Rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10655437#) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires >=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR.

  • Duration of Response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Duration of response was the time from date of response to date of progression and evaluated among participants with response. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as >=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy.

  • Overall Survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    The overall survival was evaluated using the Kaplan-Meier estimator.


Enrollment: 89
Study Start Date: March 2004
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks.
Drug: temsirolimus
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the complete and partial response rate in patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with CCI-779.

II. Determine the toxicity and safety of this drug in these patients. III. Correlate the degree of activation of P13/AKT/mTOR pathway and levels of CDK inhibitors with response in patients treated with this drug.

IV. Correlate CCI-779 induced inactivation of mTOR with response in these patients.

OUTLINE: Patients are stratified according to disease (aggressive lymphoma [group A] vs follicular lymphoma [group B] vs small lymphocytic lymphoma or chronic lymphocytic leukemia [group C]).

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks.

  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 B-cell non-Hodgkin's lymphoma, including the following subtypes:

    • Aggressive B-cell lymphoma (Group A)

      • Diffuse large B-cell lymphoma
      • Transformed lymphoma
    • Follicular lymphoma (Group B)
    • Small lymphocytic lymphoma

      • Chronic lymphocytic leukemia (CLL) (Group C)
      • Other B-cell small lymphocytic disorders
  • No mantle cell lymphoma
  • No potentially curative treatment options because of lack of response, relapse, or ineligibility
  • Relapsed or refractory disease
  • Patients with refractory disease (i.e., less than a partial response to the last treatment) must have received no more than 3 prior regimens (group A)
  • Patients with sensitive disease (i.e., at least a partial response to the last treatment) must have received no more than 4 prior regimens (group A)
  • Patients who have failed prior autologous transplantation are eligible (group A)

    • No more than 5 prior regimens (groups B and C)
    • The salvage regimen, conditioning regimen, and any maintenance therapy are considered 1 regimen
  • Prior rituximab or alemtuzumab is not considered prior therapy
  • No limitation to the amount of prior radiotherapy
  • No CNS involvement
  • Performance status: ECOG 0-2 OR Karnofsky 60-100%
  • Life expectancy more than 3 months
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No prior allergic reactions attributed to compounds of similar chemical or biological composition to CCI-779
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix Completed therapy and considered < 30% risk of relapse
  • No other concurrent uncontrolled illness
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No concurrent prophylactic hematopoietic colony-stimulating factors
  • No concurrent pegfilgrastim
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • More than 4 weeks since prior radiotherapy and recovered
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent unconventional therapies, food, or vitamin supplements containing Hypericum perforatum (St. John's wort)
  • No other concurrent known inducers of CYP3A4
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • Measurable disease*

    • At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan [Note: *Only bone marrow or peripheral blood involvement required for CLL and Waldenstrom's macroglobulinemia ]
  • Absolute neutrophil count >= 1,000/mm3
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • AST and ALT =< 2.5 times ULN
  • Creatinine =< 1.5 times ULN
  • Fasting cholesterol =< 350 mg/dL
  • Fasting triglycerides =< 400 mg/dL
  • Platelet count >= 50, 000/mm3 (> 20,000/mm3 for patients with thrombocytopenia due to bone marrow involvement)
  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: NCT00290472

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Evanston Hospital CCOP
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Adventist La Grange Memorial Hospital
La Grange, Illinois, United States, 60525
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States, 46845
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Michigan
Oncology Care Associates PLLC
Saint Joseph, Michigan, United States, 49085
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Investigators
Principal Investigator: Sonali Smith University of Chicago
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00290472     History of Changes
Obsolete Identifiers: NCT00084474
Other Study ID Numbers: NCI-2009-00047, NCI-2009-00047, CDR0000365314, NCI-6199, 12983A, 6199, 6199, N01CM62201, N01CM62202, P30CA014599
Study First Received: February 10, 2006
Results First Received: August 19, 2013
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Neoplasms
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, B-Cell, Marginal Zone
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014