Brief Title
Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia
Official Title
A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias
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.
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose and recommended phase II dose
Secondary Outcome
Antitumor activity
Condition
Blastic Phase Chronic Myelogenous Leukemia
Intervention
bortezomib
Study Arms / Comparison Groups
Arm I
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
36
Start Date
January 2004
Primary Completion Date
March 2006
Eligibility 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
Gender
All
Ages
1 Year - 21 Years
Accepts Healthy Volunteers
No
Contacts
Terzah Horton, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00077467
Organization ID
NCI-2012-01809
Secondary IDs
ADVL0317
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Terzah Horton, Principal Investigator, COG Phase I Consortium
Verification Date
June 2013