A Phase I Study of the Hsp90 Inhibitor 17-DMAG (Alvespimycin) in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), and B-cell Prolymphocytic Leukemia (B-PLL)

Inclusion Criteria:

- Patients must have histologically confirmed B-CLL/SLL or a B-PLL according to 2008
World Health Organization (WHO) diagnostic criteria

- Patients must meet one or more of the following modified indications for treatment as
described in the 2008 International Workshop on CLL (IWCLL) guidelines for the
diagnosis and treatment of CLL:

- Progressive disease, marked splenomegaly, and/or lymphadenopathy, or need to
de-bulk disease for future allogeneic transplantation

- Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count <
100,000/mm^3)

- Unexplained weight loss exceeding 10% of body weight over the past 6 months

- Fatigue grade 2 or 3 as measured by Cancer Therapy Evaluation Program (CTEP)
Active Version

- Fevers > 100.5º F OR night sweats for > 2 weeks without evidence of infection

- Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period
or a doubling time of < 6 months

- Patients must have received at least one prior therapy that includes either
fludarabine or equivalent nucleoside analogue, or an alternative regimen if a
contra-indication (i.e. autoimmune hemolytic anemia) or patient desire not to receive
fludarabine exists

- Children are excluded from this study but may be eligible for future pediatric trials

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 12 weeks

- Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X institutional ULN

- Creatinine within normal institutional limits

- Creatinine clearance >= 50 mL/min/1.73 for patients with creatinine levels above
institutional normal

- QTc < 500 msec

- Left ventricular ejection fraction (LVEF) > 40% by multi gated acquisition scan
(MUGA)

- No history of serious ventricular arrhythmia

- No myocardial infarction or active ischemic heart disease within the past year

- No New York Heart Association (NYHA) class III or IV congestive heart failure

- No poorly controlled angina

- No uncontrolled dysrhythmia requiring medication

- No left bundle branch block

- No history of congenital long QT syndrome

- Pulse oximetry at rest or on exercise > 88%

- No symptomatic pulmonary disease (Asthma or COPD that is controlled is acceptable)

- Women of childbearing potential (WOCP) are required to have negative pregnancy test
(serum) within 10-14 days and within 24 hours prior to the first dose of 17-DMAG;
further, WOCP and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) for a time frame of 14 days prior to study entry
and for the duration of study participation; should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, the
treating physician should be notified immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier;
corticosteroids alone will not be considered prior therapy, but must be discontinued
at least 24 hours prior to the first day of 17-DMAG administration unless continued
for indications other than the primary malignancy

- Patients may not be receiving any other investigational agents

- Patients with known central nervous system involvement should be excluded from this
clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 17-DMAG

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection requiring iv antibiotics, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements

- Pregnant women are excluded from this study because 17-DMAG is an agent with the
potential for teratogenic or abortifacient effects; because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with 17-DMAG, breastfeeding should be discontinued if the mother is treated
with 17-DMAG

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
17-DMAG