Adult Acute Promyelocytic Leukemia (M3)Phase 1NCT00005064
PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome
A Phase 1 study testing bortezomib in people with Adult Acute Promyelocytic Leukemia (M3) and Blastic Phase Chronic Myelogenous Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study the effectiveness of PS-341 in treating patients who have refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia in blast phase, or myelodysplastic syndrome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Promyelocytic Leukemia (M3), Blastic Phase Chronic Myelogenous Leukemia, Previously Treated Myelodysplastic Syndromes
- What is being tested?
- bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2000to Oct 2002
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- AML, ALL, or high-risk MDS (R-AEB or RAEB-t) that has:
- Not responded (no CR) to initial induction chemotherapy, or
- Recurred after an initial CR of < 1 year, or
- Recurred after an initial CR of > 1 year and failed to respond to an initial re-induction attempt, or
- Recurred more than once, OR
- Chronic myeloid leukemia in myeloid blast phase
Show all 17Show fewer
- Patients with CML blast phase may receive PS-341 as their first therapy for blast phase or after failing other treatments for blast phase
- Patients with refractory or relapsed acute promyelocytic leukemia are eligible provided they have failed an ATRA-containing regimen
- Patients who are likely to benefit from allogeneic bone marrow transplantation (i.e., age < 60 years of physiological age with histocompatible donor) should be excluded from this study unless such therapy is not feasible
- ECOG performance status =< 52 (Karnofsky >= 50%)
- Total bilirubin < 1.6 mg/ml
- ALT or AST =< 2.5 times the institutional upper limit of normal
- Creatinine < 1.6 mg/ml or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy; use of hydroxyurea on patients with rapidly proliferative disease (i.e., absolute peripheral blood blast count >= 5 x 10^9/L, and increasing by >= 1 x 10^9/L/24 hrs) is allowed up to 24 hours prior to the start of therapy with PS-341
- The effects of PS-341 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Because the potential risk of toxicity in nursing infants secondary to PS-341 treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued if the mother is treated with PS-341
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients undergoing therapy with other investigational agents
- Patients with known brain metastases or CNS disease should be excluded from this clinical trail because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia
- HIV-positive patients receiving, anti-retroviral thearpy (HAART) are excluded from the study because of possible pharmacokinetic interactions; appropriate studies will be undertaken in patients receiving, HAART therapy when indicated
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of PS-341 in Acute Myeloid Leukemias, Myelodysplastic Syndromes and Chronic Myeloid Leukemia in Blast Phase
Phase I trial to study the effectiveness of PS-341 in treating patients who have refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia in blast phase, or myelodysplastic syndrome. PS-341 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of PS-341 in patients with refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase.
II. Assess the plasma pharmacology of this drug, its ability to inhibit proteasome function and to accelerate apoptosis in circulating blasts in this patient population.
III. Assess the antileukemic effects of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
Cohorts of 2 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose level associated with toxicity probability closest to 0.2 after 30 patients are treated.
- Conditions
- Adult Acute Promyelocytic Leukemia (M3), Blastic Phase Chronic Myelogenous Leukemia, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts
- Being tested
- bortezomib
- Medical subject headings
- Leukemia, Promyelocytic, Acute, Blast Crisis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts
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
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bortezomib) | Experimental | Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression. Receives: Drug: bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence of greater or equal grade 3 toxicity
Graded using the NCI CTC version 2.0.
Measured: 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2004 (estimated)
- Study startFeb 2000
- Primary completionOct 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Acute Promyelocytic Leukemia (M3)Studies 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
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jorge Cortes, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005064
- Sponsor's protocol ID
- NCI-2012-02322
- Other IDs
- DM 99-245, U01CA062461, CDR0000067668
- Status last verified
- Jan 2013
- First submitted
- 6 Apr 2000
- Last updated
- 23 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of PS-341 in Acute Myeloid Leukemias, Myelodysplastic Syndromes and Chronic Myeloid Leukemia in Blast Phase
- ClinicalTrials.gov ID
- NCT00005064
- Acronym / sponsor ID
- NCI-2012-02322
- Conditions
- Adult Acute Promyelocytic Leukemia (M3), Blastic Phase Chronic Myelogenous Leukemia, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2000
- Primary completion
- Oct 2002 (actual)
- First posted
- 2 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.
Phase I trial to study the effectiveness of PS-341 in treating patients who have refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia in blast phase, or myelodysplastic syndrome. PS-341 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of PS-341 in patients with refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase.
II. Assess the plasma pharmacology of this drug, its ability to inhibit proteasome function and to accelerate apoptosis in circulating blasts in this patient population.
III. Assess the antileukemic effects of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
Cohorts of 2 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose level associated with toxicity probability closest to 0.2 after 30 patients are treated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bortezomib) | Experimental | Drug: bortezomibPatients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- AML, ALL, or high-risk MDS (R-AEB or RAEB-t) that has:
- Chronic myeloid leukemia in myeloid blast phase
- Patients with refractory or relapsed acute promyelocytic leukemia are eligible provided they have failed an ATRA-containing regimen
- Patients who are likely to benefit from allogeneic bone marrow transplantation (i.e., age < 60 years of physiological age with histocompatible donor) should be excluded from this study unless such therapy is not feasible
- ECOG performance status =< 52 (Karnofsky >= 50%)
Key exclusion criteria (4 listed)
- Patients undergoing therapy with other investigational agents
- Patients with known brain metastases or CNS disease should be excluded from this clinical trail because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia
- HIV-positive patients receiving, anti-retroviral thearpy (HAART) are excluded from the study because of possible pharmacokinetic interactions; appropriate studies will be undertaken in patients receiving, HAART therapy when indicated
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 | Treatment (bortezomib) |
Primary outcome
The occurrence of greater or equal grade 3 toxicity
Time frame: 35 days
Graded using the NCI CTC version 2.0.
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 23 Jan 2013.
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.
Jorge Cortes principal investigator
M.D. Anderson Cancer Center
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 in people with Adult Acute Promyelocytic Leukemia (M3) and Blastic Phase Chronic Myelogenous Leukemia, 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 17 inclusion and 4 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 23 Jan 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?
The occurrence of greater or equal grade 3 toxicity (time frame: 35 days). 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 23 Jan 2013.