PRIMARY OBJECTIVES:~I. To determine the maximum tolerated dose (MTD) of PS-341 (Velcade, Bortezomib) in combination with 17-allyamino-17-demethoxygeldanamycin (17-AAG) in patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).~II. To determine the MTD of PS-341 in combination with 17-AAG in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL).~III. To define the specific toxicities and the dose limiting toxicity (DLT) of PS-341 in combination with 17-AAG in the treatment of patients with relapsed or refractory hematologic malignancies.~SECONDARY OBJECTIVES:~I. To determine the pharmacokinetics of 17-AAG alone and in combination with PS-341 in patients with AML, ALL, CLL, and NHL.~II. To evaluate 20S proteasome inhibition following combination therapy with 17-AAG and PS-341 in patients with AML, ALL, CLL, and NHL.~III. To assess the relationship between FLT3 mutational status and leukemic cell response to PS-341 and 17-AAG in patients with AML.~IV. To assess the relationship between Bcl-2 over-expression and response to 17-AAG and PS-341 in patients with AML and NHL.~V. To evaluate the effects of the combination of PS-341 and 17-AAG on Hsp90 and NF-kappaB and their downstream targets including Hsp70, Akt, phosphorylated Akt, p21, and caspases 3 and 9 in patient-derived primary AML and NHL cells.~OUTLINE: This is a dose-escalation study. Patients are stratified according to diagnosis (acute myeloid leukemia [AML] or acute lymphoblastic leukemia vs chronic lymphoctyic leukemia or non-Hodgkin's lymphoma [NHL]).~Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) intravenously (IV) over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses.~Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation.Cohorts of 3-6 patients with receive escalating doses of 17-AAG and bortezomib 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.~After the MTD is determined, an additional 20 patients (10 per stratum with AML or follicular NHL) are enrolled and receive 17-AAG and bortezomib as above at the MTD.
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin and bortezomib in treating patients with relapsed or refractory hematologic cancer. 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving 17-N-allylamino-17-demethoxygeldanamycin together with bortezomib may kill more cancer cells.