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

Malignant Neoplasm Clinical Trial

Official title:

A Phase II Study of CCI-779 in B-cell Lymphoma and CLL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00290472
• Other study ID #: NCI-2009-00047
• Secondary ID: NCI-2009-00047CD
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2006
• Last updated: May 7, 2014
• Start date: March 2004
• Est. completion date: April 2010

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00084474

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• B-cell Chronic Lymphocytic Leukemia
• Burkitt Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Non-Hodgkin
• Malignant Neoplasm
• Neoplasms
• 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
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• temsirolimus

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Evanston Hospital CCOP	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	M D Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Adventist La Grange Memorial Hospital	La Grange	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Oncology Care Associates PLLC	Saint Joseph	Michigan
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Overall Response Rate	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.	Up to 6 years	No
Primary	Duration of Response	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.	Up to 6 years	No
Primary	Overall Survival	The overall survival was evaluated using the Kaplan-Meier estimator.	Up to 6 years	No