RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Monoclonal antibodies may kill cancer cells that are left after chemotherapy. Giving 17-N-allylamino-17-demethoxygeldanamycin with or without rituximab may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given with or without rituximab in treating patients with relapsed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered alone or in combination with rituximab in patients with relapsed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia.
• Determine the pharmacology of this combination regimen in these patients.

Secondary

• Determine the toxicity and preliminary efficacy of 17-AAG administered as a single agent and in combination with rituximab in these patients.
• Determine the immunologic effects of this combination regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Patients receive 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15 and 18 (course 1). Patients achieving ≥ 25% reduction in measurable disease after course 1 receive an additional course of single-agent 17-AAG approximately 10 days later in the absence of disease progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease. Patients failing to achieve a 25% reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15, 18, and 22; and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG as a single agent or in combination with rituximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 2 months and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

• Biological: rituximab
• Drug: tanespimycin

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia requiring treatment, defined by 1 of the following criteria:

  • Massive or progressive splenomegaly and/or lymphadenopathy
  • Anemia (hemoglobin < 11 g/dL) OR thrombocytopenia (platelet count < 100,000/mm^3)
  • Weight loss > 10% within the past 6 months
  • Grade 2 or 3 fatigue
  • Fevers > 100.5°F or night sweats for > 2 weeks with no evidence of infection
  • Progressive lymphocytosis with an increase of > 50% over a 2 month period OR an anticipated doubling time of < 6 months
• Relapsed disease
• Failed prior fludarabine or pentostatin therapy OR cannot receive fludarabine
• Lymphocyte count ≥ 5,000/mm^3

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• LVEF > 40% by MUGA
• QTc < 450 msec for male patients and < 470 msec for female patients
• Resting ejection fraction ≥ 50% by MUGA or echocardiogram
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

• No significant cardiac disease including any of the following:

  • New York Heart Association class III or IV heart failure
  • History of myocardial infarction within the past year
  • History of uncontrolled dysrhythmias
  • Active ischemic heart disease within the past year
  • Poorly controlled angina
• No history of serious ventricular arrhythmia (e.g., ventricular fibrillation, history of symptomatic or sustained ventricular tachycardia, nonsustained ventricular tachycardia > 3 beats within the past 6 months)
• No history of cardiac toxicity due to anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, or mitoxantrone hydrochloride)
• No other cardiac symptoms ≥ grade 2

Pulmonary

• DLCO (i.e., oxygen diffusion capacity) ≥ 80% by pulmonary function testing
• Resting and exercise oxygen saturation ≥ 90% by pulse oximetry
• No pulmonary symptoms ≥ grade 2
• No history of pulmonary toxicity due to bleomycin or carmustine
• No significant, symptomatic pulmonary disease requiring oxygen or medications

• No ongoing pulmonary symptoms ≥ grade 2 including any of the following:

  • Dyspnea on or off exertion
  • Paroxysmal nocturnal dyspnea
  • Significant pulmonary disease (e.g., chronic obstructive or restrictive pulmonary disease)
• No Medicare requirements for home oxygen (e.g., resting O_2 saturations ≥ 90% or desaturation to ≥ 90% with exertion)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to 17-N-allylamino-17-demethoxygeldanamycin
• No history of serious allergic reaction to eggs
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 3 months since prior rituximab and recovered

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy that potentially included the heart in the field (e.g., mantle)
• No history of chest radiation

Surgery

• Not specified

Other

• No concurrent medications that prolong or may prolong QTc
• No concurrent antiarrhythmic drugs
• No other concurrent investigational agents
• No other concurrent anticancer therapy