Rituximab, Cladribine, and Temsirolimus in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

• Status: Completed
• Trial end date: 2017-06-15
• Target enrollment: 0
• Participant gender: All

Summary

This phase I/II trial studies the side effects and best dose of temsirolimus when given together with cladribine and rituximab and to see how well it works in treating patients with newly diagnosed mantle cell lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with cladribine and rituximab may kill more cancer cells.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cladribine; Everolimus; Lenograstim; Rituximab; Sirolimus

Criteria

Inclusion Criteria:

• Histologically confirmed mantle cell lymphoma (MCL); the diagnosis must be confirmed by NCCTG pre-registration pathology review by Dr. Paul Kurtin or his designate; it is recommended that the biopsy be an excisional biopsy, but adequate core-needle biopsies will be accepted as long as they are considered adequate for registration by Dr. Kurtin or his designate; the tumor must be cyclin D-1 positive by immunohistochemistry or have evidence of a t(11;14) translocation by fluorescence based in situ hybridization (FISH) or cytogenetics

• Measurable or assessable disease, defined as at least one of the following:

• A lymph node or tumor mass that is >= 2.0 cm in at least one dimension by positron emission tomography (PET)/computed tomography (CT), CT, magnetic resonance imaging (MRI), or plain radiograph imaging

• Splenic enlargement may be used as a measurable parameter if the spleen is palpable >= 3 cm below the left costal margin

• Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, 2, or 3

• Life expectancy >= 12 weeks

• Absolute neutrophil count (ANC) >= 1,500/mm³

• Platelet count (PLT) >= 100,000/mm³

• Serum creatinine =< 2.0 mg/dL

• Serum total bilirubin (or direct bilirubin if total is abnormal) =< institutional upper limit of normal (ULN) with or without secondary liver involvement

• Serum glutamic oxaloacetic transaminase (SGOT) =< 3 x institutional ULN (exception: if there is liver involvement, SGOT must be =< 5 x institutional ULN)

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

• Willingness to return to NCCTG enrolling institution for follow-up

• Willingness to provide the blood specimens as required by the protocol

• Willingness to provide tissue specimens as required by the protocol

• 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

• Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study

Exclusion Criteria

• Any prior therapy for mantle cell non-Hodgkin lymphoma including radiation therapy; exception: patient may have undergone a splenectomy for diagnosis, cytopenia, or systematic splenomegaly

• Active or uncontrolled infection

• Any of the following cardiac conditions:

• Uncontrolled high blood pressure

• Unstable angina

• Active congestive heart failure

• Myocardial infarction =< 6 months

• Serious uncontrolled cardiac arrhythmia

• Known central nervous system (CNS) involvement

• Any of the following:

• Pregnant women or women of reproductive ability who are unwilling to use effective contraception while taking the drug and for 12 months after stopping treatment

• Nursing women

• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 12 months after stopping treatment

• Medical or psychiatric conditions which, in the opinion of the investigator, make the patient a poor risk for participation

• Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required but should be done if clinically indicated; HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

• Concurrent malignancy =< 5 years ago; exceptions: carcinoma in situ of the cervix, resected basal cell or squamous cell carcinomas of the skin, or prostate cancer that is in remission following a radical retropubic prostatectomy or radiation therapy; if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer

• Known hypersensitivity to rituximab or its components, or to murine proteins

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Prior treatment with an mTOR inhibitor

• Autologous or allogeneic stem cell transplant planned as part of initial therapy

• Receiving enzyme-inducing antiepileptic drugs (enzyme inducing anti-epileptic drugs [EIAEDs]; e.g., phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, phenobarbital, or primidone); any other potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin, glucocorticoids at greater than adrenal replacement levels, or St. John's wort; or receiving strong CYP3A4 inhibitors * Note: if these agents are discontinued, temsirolimus therapy can begin >= 7 days after discontinuation of such agent