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A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias


Phase 1
1 Year
21 Years
Not Enrolling
Both
Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia

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Trial Information

A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and recommended phase II dose

Outcome Time Frame:

Up to 21 days

Safety Issue:

Yes

Principal Investigator

Terzah Horton

Investigator Role:

Principal Investigator

Investigator Affiliation:

COG Phase I Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01809

NCT ID:

NCT00077467

Start Date:

January 2004

Completion Date:

Related Keywords:

  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Promyelocytic Leukemia (M3)
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Blast Crisis
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Promyelocytic, Acute

Name

Location

COG Phase I ConsortiumArcadia, California  91006-3776