Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed mantle cell lymphoma

- Newly diagnosed disease

- Excisional biopsy or adequate core needle biopsies allowed

- Tumor must be cyclin D-1 positive by IHC or have evidence of a t(11;14)
translocation by FISH or cytogenetics

- Measurable or assessable disease, defined as ≥ 1 of the following:

- A lymph node or tumor mass that is ≥ 2.0 cm in ≥ 1 dimension by PET/CT, CT, MRI,
or plain radiograph imaging

- Enlarged spleen that is palpable ≥ 3 cm below the left costal margin

- Diffuse infiltration of an organ (e.g., stomach, bone marrow, peripheral blood,
liver, lungs, or bowel) by lymphoma without a discrete mass (assessable only
disease)

- No known CNS involvement

PATIENT CHARACTERISTICS:

- ECOG performance status 0-3

- Life expectancy ≥ 12 weeks

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Serum creatinine ≤ 2.0 mg/dL

- Serum total bilirubin (or direct bilirubin if total is abnormal) normal with or
without secondary liver involvement

- SGOT ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN if there is liver
involvement)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study treatment

- Willing to return to NCCTG enrolling institution for follow-up

- Willing to provide blood and tissue specimens as required by the protocol

- Willing to abstain from eating grapefruit or drinking grapefruit juice

- No active or uncontrolled infection

- No cardiac conditions, including any of the following:

- Uncontrolled high blood pressure

- Unstable angina

- Active congestive heart failure

- Myocardial infarction within the past 6 months

- Serious uncontrolled cardiac arrhythmia

- No medical or psychiatric conditions which, in the opinion of the investigator, make
the patient a poor risk for participation

- No known HIV positivity

- No other malignancy within the past 5 years except carcinoma in situ of the cervix,
resected basal cell or squamous cell carcinoma of the skin, or prostate cancer that
is in remission following a radical retropubic prostatectomy or radiation therapy

- No known hypersensitivity to rituximab or its components, or to murine proteins

PRIOR CONCURRENT THERAPY:

- No prior therapy for mantle cell non-Hodgkin lymphoma, including radiation therapy

- Patients may have undergone a splenectomy for diagnosis, cytopenia, or
systematic splenomegaly

- No prior mTOR inhibitor

- At least 7 days since prior and no concurrent enzyme-inducing antiepileptic drugs
(e.g., phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, phenobarbital, or
primidone)

- At least 7 days since prior and no concurrent potent CYP3A4 inducer (e.g., rifampin,
glucocorticoids at greater than adrenal replacement levels, or St. John's wort)

- At least 7 days since prior and no concurrent strong CYP3A4 inhibitors

- No planned autologous or allogeneic stem cell transplantation as part of initial
therapy

- No concurrent combination anti-retroviral therapy for HIV-positive patients

- No other specific, concurrent treatment for prior cancer (other than hormonal
therapy)

- No concurrent glucocorticoid steroids or other immunosuppressive therapies

- Concurrent corticosteroids allowed for treatment of adrenal insufficiency, acute
allergic reactions, or as N078D 27 prophylaxis for infusion-related adverse
events

- No other concurrent investigational agent that would be considered treatment for the
primary neoplasm