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Phase I Using Velcade & Idarubicin in Elderly and Relapsed AML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00382954
Recruitment Status : Completed
First Posted : October 2, 2006
Last Update Posted : September 29, 2010
National Institutes of Health (NIH)
Information provided by:
University of Kentucky

Brief Summary:

The purpose of this study is to determine the maximal tolerated dose (MTD) of bortezomib and idarubicin given in combination to newly diagnosed AML patients >60 years or relapsed AML patients.

Another purpose of this study is to determine the dose limiting toxicities associated with bortezomib in combination with idarubicin in newly diagnosed AML patients >60 years or relapsed AML patients.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Drug: Velcade Drug: Idarubicin Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Using Bortezomib (Velcade, Formerly Known as PS-341) With Weekly Idarubicin for the Treatment of Elderly (>/= 60 Years) and Relapsed Patients With Acute Myelogenous Leukemia
Study Start Date : February 2004
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Arm Intervention/treatment
Experimental: Phase 1 escalation Drug: Velcade
velcade (4 original dosing levels with 3 modified dosing levels) I.V. on days 1, 4, 8, 11, 15, 18, 22, and 25 for 4 weeks concurrent with the Idarubicin
Other Name: Bortezomib

Drug: Idarubicin
I.V., 8, or 10 or 12 mg/m^2 weekly (days 1, 8, 15, and 22) for 4 weeks

Primary Outcome Measures :
  1. Maximum tolerated dose of bortezomib & idarubicin given in combination, with idarubicin given once weekly for 4 consecutive weeks & bortezomib given twice weekly over the same time. [ Time Frame: week 4 ]
  2. Dose limiting toxicities associated with bortezomib in combination with idarubicin. [ Time Frame: week 4 ]

Secondary Outcome Measures :
  1. Response to the combination of Idarubicin and Bortezomib. [ Time Frame: Days 18 & 50 ]
  2. Pre- & post-treatment inhibition of NF-kB activity in the malignant & normal hematopoietic cell populations. [ Time Frame: 24 hours after the initial dose of Bortezomib ]
  3. Induction of p53 levels in the malignant cell populations. [ Time Frame: 2 and 24 hours post day +1 Bortezomib ]
  4. Bortezomib PK when administered to patients with acute leukemia receiving concomitant medications that could lead to drug interactions. In the case of altered pharmacokinetics, a pharmacodynamic assay to check proteasome inhibition may also be applied. [ Time Frame: Days 1, 4, 8, 11, 15 ]
  5. Idarubicin PK in order to observe any alteration in metabolism/elimination of Idarubicin & its active metabolite idarubicinol when it is combined with Bortezomib. [ Time Frame: Days 1, 4, 8, 11, 15 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age: > 60 years of age for newly diagnosed/transformed disease; > 18 years of age for relapsed disease.
  • AML with or without antecedent hematologic disorder diagnosed by morphologic, histochemical, or cell surface marker criteria - as defined by the WHO classification (17).
  • Newly diagnosed, elderly patients who are considered unsuitable for intensive chemotherapy induction -- antecedent hematologic disorders, pre-existing myelodysplasia, trilineage dyspoiesis, unfavorable cytogenetics, or pre-existing comorbidities.
  • Untreated conditions meeting criteria the first and third criteria or patients with diagnosis as in criteria 2 who have relapsed after at least one successful induction therapy. (Relapsed patients treated on this protocol will be patients without a suitable donor for transplant or for whom transplant is not an option for other reasons.)
  • Karnofsky performance status >60.
  • Adequate cardiac function as evidenced by an ejection fraction on MUGA >/= 40, as well as no evidence of uncontrolled hypertension, New York Heart Class III/IV congestive heart failure, angina pectoris, or ventricular dysrhythmias.
  • Adequate renal function as evidenced by a calculated creatinine clearance >/= 30ml/min (Cockcroft-Gault formula).
  • Adequate pulmonary function as evidenced by room air and exercise saturations >/= 92 or DLCO >/= 40% or FEV1 >/= 60% of predicted.
  • Adequate liver function as evidenced by SGOT/SGPT less than 5 times the ULN and total Bilirubin less than 2 times the ULN except where abnormalities are directly attributable to leukemia.
  • Adequate neurologic function -- patients must be currently free of active CNS leukemia as evidenced by cytospin of CSF from lumbar puncture if there is any clinical suspicion for CNS leukemia. As well, patients must not have >/= grade 2 neuropathy by NCI common toxicity criteria (CTC), Version 3.0.
  • Prior anthracycline dose in relapsed patients must not exceed 72 mg/m^2 of idarubicin or any dose equivalent to 300 mg/m^2 of adriamycin.
  • Patients must be informed and sign a written consent.

Exclusion Criteria:

  • Patients with acute promyelocytic leukemia. Patients with uncontrolled systemic infection.
  • Patients who are known to be HIV seropositive.
  • Patients with evidence of CNS leukemia.
  • Patients who are pregnant or lactating.
  • Patients with primarily refractory disease unresponsive to a standard induction regimen.
  • Patients with a new diagnosis as per inclusion criteria 2, but for whom standard induction chemotherapy would be expected to be well tolerated and a preferred option in the opinion of the principal investigator.
  • Patients with relapsed AML, but for whom a suitable donor of stem cells exists and in whom high-dose chemotherapy with hematopoietic stem cell transplant is felt to be a better immediate alternative.
  • Patients with any clinically significant abnormality in screening blood chemistry, hematology or urinalysis results that, in the judgment of the investigator, would impede adequate evaluation of adverse events and/or response to treatment, or that requires aggressive intervention.
  • Patients with hypersensitivity to Bortezomib, boron, or mannitol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00382954

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United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, New York
University of Rochester
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Kentucky
National Institutes of Health (NIH)
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Principal Investigator: Dianna Howard, MD University of Kentucky

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Dianna Howard, MD, University of Kentucky Identifier: NCT00382954     History of Changes
Other Study ID Numbers: 03-BMT-145
First Posted: October 2, 2006    Key Record Dates
Last Update Posted: September 29, 2010
Last Verified: September 2010

Keywords provided by University of Kentucky:
Acute Myelogenous Leukemia

Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action