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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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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

Intervention / Treatment
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* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br> <br> * Other names: Torisel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Overall Survival | The overall survival was evaluated using the Kaplan-Meier estimator. | Up to 6 years |