Blastic Phase Chronic Myelogenous LeukemiaPhase 1NCT00077467
Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia
A Phase 1 study testing bortezomib, pharmacological study and laboratory biomarker analysis in people with Blastic Phase Chronic Myelogenous Leukemia and Childhood Acute Promyelocytic Leukemia (M3), run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia
- What is being tested?
- bortezomib, pharmacological study and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Mar 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 50Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
COG Phase I Consortium
Arcadia, California, 91006-3776
About this study
Official title: A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias
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.
Read the 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.
- Conditions
- Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia
- Being tested
- bortezomib, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Blast Crisis, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Drug: bortezomib; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose and recommended phase II dose
Measured: Up to 21 days
Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 3.0
Measured: Up to 2 years
Pharmacokinetics as assessed by confidence intervals (CI), area under the curve (AUC), and half-life (T ½)
Measured: Pretreatment, days 1, 8, 18-22 of course 1
Secondary outcomes (2)
Antitumor activity
Measured: Up to 2 years
Correlate apoptosis and NF-kB activation
Measured: Prestudy, days 8 and 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2004 (estimated)
- Study startJan 2004
- Primary completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Blastic Phase Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Terzah Horton, Principal investigator, COG Phase I Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00077467
- Sponsor's protocol ID
- NCI-2012-01809
- Other IDs
- ADVL0317, CDR0000350340, COG-ADVL0317, U01CA097452
- Status last verified
- Jun 2013
- First submitted
- 10 Feb 2004
- Last updated
- 5 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias
- ClinicalTrials.gov ID
- NCT00077467
- Acronym / sponsor ID
- NCI-2012-01809
- Conditions
- Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2004
- Primary completion
- Mar 2006 (actual)
- First posted
- 12 Feb 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: bortezomib, Other: pharmacological study, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (50 listed)
- Histologically confirmed leukemia of 1 of the following types:
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
Primary outcome
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
2 secondary outcomes
Antitumor activity
Time frame: Up to 2 years
Correlate apoptosis and NF-kB activation
Time frame: Prestudy, days 8 and 18
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terzah Horton principal investigator
COG Phase I Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bortezomib, pharmacological study and laboratory biomarker analysis in people with Blastic Phase Chronic Myelogenous Leukemia and Childhood Acute Promyelocytic Leukemia (M3), run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 50 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose and recommended phase II dose (time frame: Up to 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2013.