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Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: February 10, 2004
Last updated: June 4, 2013
Last verified: June 2013
This phase I trial is studying the side effects and best dose of bortezomib in treating young patients with refractory or recurrent leukemia. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

Condition Intervention Phase
Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Promyelocytic Leukemia (M3) Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Drug: bortezomib Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose and recommended phase II dose [ Time Frame: Up to 21 days ]
  • Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 3.0 [ Time Frame: Up to 2 years ]
  • Pharmacokinetics as assessed by confidence intervals (CI), area under the curve (AUC), and half-life (T ½) [ Time Frame: Pretreatment, days 1, 8, 18-22 of course 1 ]

Secondary Outcome Measures:
  • Antitumor activity [ Time Frame: Up to 2 years ]
  • Correlate apoptosis and NF-kB activation [ Time Frame: Prestudy, days 8 and 18 ]

Enrollment: 36
Study Start Date: January 2004
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES: Primary I. Determine the maximum tolerated dose and recommended phase II dose of bortezomib in children with refractory or recurrent leukemia.

II. Determine the toxic effects of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.

Secondary I. Determine, preliminarily, the antitumor activity of this drug in these patients.

II. Determine, preliminarily, the biologic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, open-label, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 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.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 1.5-36 months.


Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed leukemia of 1 of the following types:

    • Acute lymphoblastic leukemia
    • Acute myeloid leukemia
    • Chronic myelogenous leukemia in blast crisis
  • Relapsed or refractory disease
  • Immunophenotypically confirmed disease, either at initial diagnosis or relapse
  • More than 25% blasts in the bone marrow (M3 bone marrow)
  • Active extramedullary disease (except leptomeningeal disease) allowed
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life available
  • Performance status - Karnofsky 50-100% (for patients age 11 to 21)
  • Performance status - Lansky 50-100% (for patients age 10 and under)
  • Platelet count ≥ 20,000/mm^3*
  • Hemoglobin ≥ 8.0 g/dL*
  • WBC < 20,000/mm^3** (hydroxyurea for cytoreduction allowed)
  • No hyperleukocytosis (i.e., WBC > 100,000/mm^3)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 5 times ULN
  • Albumin ≥ 2 g/dL
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
  • Creatinine based on age as follows:

    • ≤ 0.8 mg/dL for patients age 5 and under
    • ≤ 1.0 mg/dL for patients age 6 to 10
    • ≤ 1.2 mg/dL for patients age 11 to 15
    • ≤ 1.5 mg/dL for patients age 16 to 21
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • Recovered from prior immunotherapy
  • At least 7 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
  • At least 7 days since prior biologic agents
  • At least 3 months since prior stem cell transplantation or rescue and no evidence of active graft-versus-host disease
  • No concurrent prophylactic G-CSF during course 1 of study
  • No concurrent immunotherapy
  • No concurrent biologic therapy
  • Recovered from prior chemotherapy
  • At least 24 hours since prior hydroxyurea for cytoreduction
  • At least 6 weeks since prior nitrosoureas
  • No concurrent chemotherapy
  • At least 7 days since prior steroids (except as premedication prior to blood product transfusion)
  • Recovered from prior radiotherapy
  • At least 2 weeks since prior small port local palliative radiotherapy
  • At least 3 months since prior total body irradiation, craniospinal irradiation, or irradiation to more than 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • No concurrent radiotherapy
  • At least 7 days since prior retinoids
  • No other concurrent investigational agents
  • No other concurrent anticancer agents
  • No concurrent anticonvulsant medications known to activate the cytochrome p450 system (e.g., phenytoin, carbamazepine, or phenobarbital)

    • Concurrent benzodiazepines and gabapentin are allowed
  Contacts and Locations
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Please refer to this study by its identifier: NCT00077467

United States, California
COG Phase I Consortium
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Terzah Horton COG Phase I Consortium
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00077467     History of Changes
Other Study ID Numbers: NCI-2012-01809
U01CA097452 ( U.S. NIH Grant/Contract )
Study First Received: February 10, 2004
Last Updated: June 4, 2013

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Blast Crisis
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Cell Transformation, Neoplastic
Neoplastic Processes
Pathologic Processes
Antineoplastic Agents processed this record on August 18, 2017