A Phase 1 Study of 17-allylamino-17-demethoxygeldanamycin (17-AAG) (NSC 330507; IND 57,966) and Rituximab in Patients With Relapsed B-cell Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria:

- 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

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- More than 12 weeks

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 2.0 mg/dL

- 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

- 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)

- 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

- More than 3 months since prior rituximab and recovered

- 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 prior radiotherapy that potentially included the heart in the field (e.g., mantle)

- No history of chest radiation

- No concurrent medications that prolong or may prolong QTc

- No concurrent antiarrhythmic drugs

- No other concurrent investigational agents

- No other concurrent anticancer therapy