Status:

TERMINATED

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

Lead Sponsor:

National Cancer Institute (NCI)

Conditions:

Adult Acute Basophilic Leukemia

Adult Acute Eosinophilic Leukemia

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief 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...

Detailed Description

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 re...

Eligibility Criteria

Inclusion

  • 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

Exclusion

    Key Trial Info

    Start Date :

    April 1 2005

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    Estimated Enrollment :

    74 Patients enrolled

    Trial Details

    Trial ID

    NCT00103272

    Start Date

    April 1 2005

    Last Update

    June 4 2013

    Active Locations (1)

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    Page 1 of 1 (1 locations)

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    Ohio State University Medical Center

    Columbus, Ohio, United States, 43210