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Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00077467
First received: February 10, 2004
Last updated: December 13, 2012
Last verified: December 2012
History of Changes
  Purpose

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: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE 1 STUDY OF PS-341 (VELCADE, BORTEZOMIB) IN PEDIATRIC PATIENTS WITH REFRACTORY/RECURRENT LEUKEMIAS

Resource links provided by NLM:

Drug Information available for: Bortezomib
U.S. FDA Resources

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 ] [ Designated as safety issue: Yes ]
  • Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor activity [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Correlate apoptosis and NF-kB activation [ Time Frame: Prestudy, days 8 and 18 ] [ Designated as safety issue: No ]

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
  • VELCADE
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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077467

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Terzah Horton Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00077467     History of Changes
Other Study ID Numbers: NCI-2012-01809, ADVL0317, U01CA097452, CDR0000350340
Study First Received: February 10, 2004
Last Updated: December 13, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Blast Crisis
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
 Hematologic Diseases
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013