17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer

• Status: Terminated
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Bortezomib

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