Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia

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: NCT00077467
Recruitment Status : Completed
First Posted : February 12, 2004
Last Update Posted : June 5, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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 or disease Intervention/treatment 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

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
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
Study Start Date : January 2004
Actual Primary Completion Date : March 2006

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Maximum tolerated dose and recommended phase II dose [ Time Frame: Up to 21 days ]
  2. Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 3.0 [ Time Frame: Up to 2 years ]
  3. 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 :
  1. Antitumor activity [ Time Frame: Up to 2 years ]
  2. Correlate apoptosis and NF-kB activation [ Time Frame: Prestudy, days 8 and 18 ]

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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

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): 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

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00077467     History of Changes
Other Study ID Numbers: NCI-2012-01809
U01CA097452 ( U.S. NIH Grant/Contract )
First Posted: February 12, 2004    Key Record Dates
Last Update Posted: June 5, 2013
Last Verified: June 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