A Phase II Study of CCI-779 in B-cell Lymphoma and CLL
A Phase II Study of CCI-779 in B-cell Lymphoma and CLL
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.
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.
Inclusion Criteria:
Histologically or cytologically confirmed B-cell non-Hodgkin's lymphoma, including the following subtypes:
Aggressive B-cell lymphoma (Group A)
Follicular lymphoma (Group B)
Small lymphocytic lymphoma
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)
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*
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)