17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer
Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7)
About this trial
This is an interventional treatment trial for Adult Acute Basophilic Leukemia
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies: Acute myeloid leukemia or acute lymphoblastic leukemia Not a candidate for potentially curative therapy WBC ≤ 10,000/mm^3 OR WBC ≤ 40,000/mm^3 that is stable for 5 days (hydroxyurea allowed) No acute promyelocytic leukemia Non-Hodgkin's lymphoma (NHL), including 1 of the following subtypes: Small lymphocytic lymphoma Marginal zone lymphoma Lymphoplasmacytic lymphoma Follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma Anaplastic large cell lymphoma Peripheral T-cell lymphoma Extranodal NK/T cell lymphoma (nasal and nasal type) Enteropathy-type T-cell lymphoma Hepatosplenic T-cell lymphoma Angioimmunoblastic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Chronic lymphocytic leukemia (CLL) Patients with NHL or CLL must meet the following criteria: Ineligible for, or refused potentially curative stem cell transplantation Transformed lymphoma/Richter's transformation, defined as the transformation of low-grade lymphoma, including follicular lymphoma, CLL, or small lymphocytic lymphoma to high-grade lymphoma (i.e., diffuse large cell lymphoma) allowed at time of transformation Evidence of ≥ 50% bone marrow involvement at the time of enrollment OR tumor tissue accessible for biopsy (for patients enrolled after the maximum tolerated dose [MTD] is determined) Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 Relapsed or refractory disease Willing to undergo serial bone marrow biopsy (for patients enrolled after the MTD is determined) No untreated or active CNS leukemia or lymphoma Performance status - ECOG 0-2 At least 12 weeks Bilirubin ≤ 1.5 mg/dL AST and ALT ≤ 2.5 times upper limit of normal Creatinine ≤ 2.0 mg/dL No uncontrolled cardiac disease No New York Heart Association class III-IV symptomatic congestive heart failure No unstable angina pectoris No serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation > 3 beats in a row) within the past 6 months No other uncontrolled cardiac arrhythmia or requiring antiarrhythmic drugs No myocardial infarction within the past year No active ischemic heart disease within the past year No congenital long QT syndrome No left bundle branch block QTc ≥ 450 msec (for men) or 470 (for women) on ECG/EKG No history of LVEF < 50% by MUGA or echocardiogram Resting ejection fraction ≥ 50% by MUGA or echocardiogram No prior history of cardiac toxicity after receiving anthracycline therapy (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, or mitoxantrone hydrochloride) No uncontrolled pulmonary disease No symptomatic pulmonary disease requiring oxygen or medications DLCO (i.e., oxygen diffusion capacity) ≥ 80% on pulmonary function testing Resting and exercise oxygen saturation ≥ 90% by pulse oximetry No ongoing pulmonary symptoms ≥ grade 2 including any of the following: Dyspnea on or off exertion Paroxysmal nocturnal dyspnea Significant pulmonary disease including chronic obstructive or restrictive pulmonary disease No prior history of pulmonary toxicity after bleomycin or carmustine No Medicare requirement for home oxygen (e.g., Resting O_2 saturation ≥ 90% or desaturation to ≥ 90% with exertion) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No preexisting sensory or motor peripheral neuropathy ≥ grade 2 No history of allergic reaction to eggs No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness Prior stem cell transplantation for relapsed or refractory disease allowed At least 2 weeks since prior immunotherapy and recovered At least 2 weeks since prior chemotherapy (excluding hydroxyurea) and recovered No other concurrent chemotherapy No concurrent routine corticosteroids except for treatment of other medical problems (e.g., pulmonary, rheumatologic, or adrenal disorders) At least 2 weeks since prior radiotherapy and recovered No prior radiotherapy that potentially included the heart in the field (e.g., mantle) No prior history of chest radiation No concurrent palliative radiotherapy At least 2 weeks since prior investigational therapy Prior bortezomib allowed No other concurrent commercial or investigational agents or therapies for the malignancy
Sites / Locations
- Ohio State University Medical Center
Arms of the Study
Arm 1
Experimental
Treatment (17-AAG and bortezomib)
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) 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.