CCI-779 in Treating Patients With Mantle Cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of CCI-779 in treating patients who have mantle cell non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

Detailed Description
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OBJECTIVES: I. Determine the objective responses in patients with previously treated mantle cell non-Hodgkin's lymphoma treated with CCI-779. II. Determine the toxic effects of this drug in these patients. III. Determine whether this drug inhibits cell proliferation pathways in these patients. OUTLINE: 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 with stable disease receive a maximum of 6 courses. Patients with partial response receive a maximum of 12 courses. Patients with complete response (CR) receive 2 additional courses beyond CR. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

Official Title
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A Phase II Study of CCI-779 in Previously Treated Patients With Mantle Cell Non-Hodgkin's Lymphoma

Conditions
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Recurrent Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed mantle cell non-Hodgkin's lymphoma (MCL) Relapsed, refractory, or stable disease after prior chemotherapy, radiotherapy, or immunotherapy Unidimensionally measurable lymph node or lesion At least 2.0 cm by CT scan or MRI OR at least 1.5 cm by physical exam One of the following measurement parameters may be used: Splenic enlargement may be used as a measurement parameter if spleen is palpable at least 3.0 cm across left costal margin Malignant lymphocytosis may be used as a measurement parameter if absolute lymphocyte count is at least 5,000/mm^3 No known CNS involvement (parenchymal mass or leptomeningeal involvement) Performance status - ECOG 0-2 At least 3 months See Disease Characteristics Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 8 g/dL Total bilirubin ≤ 1.5 times upper limit of normal (ULN) Direct bilirubin ≤ 1.5 times ULN AST ≤ 3 times ULN (5 times ULN if liver metastases are present) Creatinine ≤ 2 times ULN No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Cholesterol ≤ 350 mg/dL Triglycerides ≤ 400 mg/dL HIV negative No other active malignancy requiring treatment or that would preclude study participation No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation See Disease Characteristics Prior high-dose therapy with stem cell transplantation allowed At least 7 days since prior immunotherapy or other non-myelosuppressive biologic response modifiers See Disease Characteristics See Biologic therapy At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas or mitomycin) No other concurrent chemotherapy for MCL Concurrent corticosteroids for adrenal insufficiency allowed See Disease Characteristics At least 3 weeks since prior radiotherapy No concurrent radiotherapy for MCL Any number of prior treatments allowed No other concurrent investigational or commercial agents for MCL No concurrent drugs that induce cytochrome p450 (e.g., carbamazepine, phenobarbital, phenytoin, ketoconazole, diltiazem, rifampin, terfenadine, cisapride, astemizole, or pimozide) No concurrent immunosuppressive therapies

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: Treatment<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 with stable disease receive a maximum of 6 courses. Patients with partial response receive a maximum of 12 courses. Patients with CR receive 2 additional courses beyond CR. | Drug: temsirolimus<br>* Given IV<br>* Other names: Torisel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve a confirmed CR or PR during the first 24 weeks of treatment defined by the International Workshop criteria | The proportion will be evaluated separately for each dose group. The proportion of patients who achieve a confirmed CR or PR, or success, will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | The distribution of time to progression will be estimated using the method of Kaplan-Meier. | Time from registration to the time of progression, assessed up to 5 years | 
| Overall survival | The distribution of overall survival will be estimated using the method of Kaplan-Meier. | Time from registration to death due to any cause, assessed up to 5 years | 
| Progression-free survival | The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. | Time from registration to progression or death due to any cause, assessed up to 5 years | 
| Duration of response |  | From the date of study registration until the date of progression in the subset of patients who respond, assessed up to 5 years |