Cladribine in Patients With Mantle Cell Lymphoma

OBJECTIVES: I. Determine the efficacy of cladribine (2-chlorodeoxyadenosine; 2-CdA) as
treatment for mantle cell lymphoma (MCL) either as initial therapy or for
relapsed/refractory disease. II. Determine by flow cytometry immunophenotyping of blood
lymphocytes the number of patients with peripheral blood involvement at the time of
diagnosis and compare the presence or absence of peripheral blood involvement with response
data. III. Detect rearrangements involving the bcl-1 gene and immunoglobulin heavy chain
locus by molecular techniques (e.g., polymerase chain reaction, Southern blotting, or in
situ hybridization), and compare these results with immunohistochemical demonstration of
bcl-1 protein expression. VI. Determine the proliferative rate of MCL by
immunohistochemistry and DNA content flow cytometry. V. Summarize the toxic effects
associated with this treatment.

OUTLINE: Patients receive cladribine (2-chlorodeoxyadenosine; 2-CdA) daily for 5 days every
4 weeks for a maximum of 6 courses; response is assessed after every 2 courses. Patients in
complete remission or with stable disease discontinue treatment and are followed; those with
disease progression at any time are removed from study. Patients are followed every 2 months
for 1 year, every 4 months for 1 year, every 6 months for 1 year, and annually for 2 years.

DISEASE CHARACTERISTICS: Histologically confirmed mantle cell lymphoma (MCL) requiring
therapy NCCTG pathology review required - Repeat biopsy is required for previously treated
patients with previously biopsy proven MCL who relapse after achieving a partial or
complete remission - Rebiopsy is not required for patients with: Progression of previously
biopsy proven MCL who have not received therapy since the diagnostic biopsy OR Previously
biopsy proven MCL who progress or achieve less than a partial remission following initial
therapy Measurable or evaluable disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-3 Life expectancy: At
least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hepatic: Bilirubin normal AST no greater than 3 times normal (5 times
normal with liver involvement) Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular:
No uncontrolled hypertension No unstable angina No active congestive heart failure No
myocardial infarction within 6 months No serious uncontrolled arrhythmia Other: No active
or uncontrolled infection No HIV antibody No medical or psychiatric condition that
precludes participation No malignancy in the past 5 years, except 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 No
pregnant or nursing women Negative pregnancy test required of fertile women within 7 days
prior to entry Effective contraception required of fertile patients throughout study and
at least 30 days thereafter

PRIOR CONCURRENT THERAPY: Recovered from any reversible acute toxic effects of previous
therapy Biologic therapy: Not specified Chemotherapy: At least 4 weeks since chemotherapy
(8 weeks since nitrosoureas or mitomycin) No prior fludarabine, pentostatin, or cladribine
Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to greater than 25%
of bone marrow Surgery: Not specified