Acute Myelogenous LeukemiaPhase 2NCT01736943
Bortezomib and Doxil for the Treatment of Patients With Acute Myelogenous Leukemia
A Phase 2 study testing Bortezomib and Doxil in people with Acute Myelogenous Leukemia, run by Joseph Tuscano at 1 site in United States.
Trial summary
The purpose of this study is to determine whether bortezomib in combination with doxil/lipodox is effective in the treatment of Acute Myeloid Leukemia. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- Bortezomib and Doxil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2012to 20 May 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Female subjects must be either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of SQ VELCADE, or agree to completely abstain from heterosexual intercourse.
- Male subjects, even if surgically sterilized must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- Adults (age 18 to 80) with AML, excluding the M3 subtype, that are not likely to respond to conventional therapy
- Bone marrow and peripheral blood studies must be available for confirmation of diagnosis.
- Performance status of 60% or greater by the Karnofsky scale
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- A minimum of 4 weeks must have elapsed since the completion of prior chemotherapy.
- Patients may have had autologous transplant.
- There are no minimum hematological parameter requirements prior to the first two cycles, as patients with AML and myelodysplastic syndrome (MDS) are understood to have low absolute neutrophil count (ANC) and platelet counts when the disease is active. However, patients with white blood cell count (WBC) greater than 30,000 will receive hydroxyurea to reduce the WBC count to below 30,000 at which point they may begin treatment.
- A pretreatment calculated creatinine clearance (absolute value) of ≥ 40 ml/minute or serum creatinine of < 1.5 x upper limit of normal is required.
- Patients must have a serum bilirubin ≤1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤2.5 times the institutional upper limits of normal.
Who cannot join
- There is no specific platelet and absolute neutrophil count that will exclude patients from this study given the natural history of AML.
- Patient has greater than or equal to Grade 2 peripheral neuropathy
- Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant. An left ventricular ejection fraction (LVEF) must be > 50
- Patient has hypersensitivity to VELCADE, boron, or mannitol.
- Female subject is pregnant or lactating.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
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- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
- Patients with active/uncontrolled central nervous system (CNS) leukemia
- Patients eligible, at the time of starting treatment, for curative therapeutic approaches (such as allogeneic transplant) are not eligible for the trial.
- Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study other than hydroxyurea for control of counts.
- Human Immunodeficiency Virus (HIV)-positive.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase II Trial of the Combination of Subcutaneous (SQ) Bortezomib and Pegylated Liposomal Doxorubicin (PLD or Doxil or LipoDox) for the Treatment of Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML)
The purpose of this study is to determine whether bortezomib in combination with doxil/lipodox is effective in the treatment of Acute Myeloid Leukemia.
Read the detailed description
Acute myeloid leukemia (AML) remains largely incurable despite advances that have been made in recent years into increasing the complete response (CR) rates. In elderly patients (over the age of 60), CR rates are lower, 40 to 50%, and long term disease-free and overall survival is less than 10%. The therapeutic options for relapsed/refractory AML are significantly limited. Bortezomib has shown promising activity in patients with advanced hematologic malignancies, including those with leukemia and non-Hodgkin's lymphoma.
Given the available data suggesting efficacy of bortezomib in combination with doxil in patients with relapsed multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and Non Hodgkin's lymphoma (NHL) as well as the known sensitivity of AML to anthracyclines and in vitro data demonstrating the sensitivity of multiply resistant AML cells to bortezomib, we are proposing the use of this combination in patients with relapsed/refractory AML or elderly patients who are not candidates for standard induction therapy.
Using the subcutaneous formulation of bortezomib would provide patients with reduced neurotoxicity and easier schedule due to decreased time in the infusion room and it would decrease overall cost of care.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- Bortezomib, Doxil
- Keywords
- Bortezomib, Doxil
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Bortezomib will be given twice a week subcutaneously (under the skin) for two weeks in every 3 week cycle.
DoxilDrug
Also called LipoDox; pegylated liposomal doxorubicin
Doxil or LipoDox will also be given through a venous catheter (inside your vein). Doxil or LipoDox will be given over 60 to 90 minutes on Day 4 of every 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib + Doxil | Experimental | Bortezomib will be given subcutaneously at 1.5mg/m2 on days 1, 4, 8 and 11 of a 3 week cycle. Doxil will be administered once every three weeks as a single intravenous infusion at a dose of 40 mg/m2 (day 4 of each cycle). Receives: Drug: Bortezomib; Drug: Doxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
The time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.
Measured: Up to 2 years
Secondary outcomes (2)
Overall Survival
Overall survival wil be measured as the time from start of treatment to the Date of death or the last date the patient was known to be alive
Measured: Up to two years
Toxicity Information Recorded Will Include the Type, Severity, Time of Onset, Time of Resolution, and the Probable Association With the Study Regimen.
Toxicity will be evaluated based on the standard NCI Common Toxicity Criteria for Adverse Effects CTCAE) V.4.0 grading criteria.
Measured: Up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2012 (estimated)
- Study start19 Dec 2012
- Primary completion20 May 2019
- Study completion20 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Tuscano
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor-investigator, Joseph Tuscano, University of California, Davis
- Investigators
- Joseph Tuscano, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01736943
- Sponsor's protocol ID
- 322070
- Other IDs
- UCDCC#230, X05385
- Status last verified
- Feb 2021
- First submitted
- 26 Nov 2012
- Last updated
- 24 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of the Combination of Subcutaneous (SQ) Bortezomib and Pegylated Liposomal Doxorubicin (PLD or Doxil or LipoDox) for the Treatment of Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML)
- ClinicalTrials.gov ID
- NCT01736943
- Acronym / sponsor ID
- 322070
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Bortezomib, Doxil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Joseph TuscanoUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- 19 Dec 2012 (actual)
- Primary completion
- 20 May 2019 (actual)
- Study completion
- 20 May 2019 (actual)
- First posted
- 29 Nov 2012 (estimated)
- Results
- Posted 24 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether bortezomib in combination with doxil/lipodox is effective in the treatment of Acute Myeloid Leukemia.
Detailed description
Acute myeloid leukemia (AML) remains largely incurable despite advances that have been made in recent years into increasing the complete response (CR) rates. In elderly patients (over the age of 60), CR rates are lower, 40 to 50%, and long term disease-free and overall survival is less than 10%. The therapeutic options for relapsed/refractory AML are significantly limited. Bortezomib has shown promising activity in patients with advanced hematologic malignancies, including those with leukemia and non-Hodgkin's lymphoma.
Given the available data suggesting efficacy of bortezomib in combination with doxil in patients with relapsed multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and Non Hodgkin's lymphoma (NHL) as well as the known sensitivity of AML to anthracyclines and in vitro data demonstrating the sensitivity of multiply resistant AML cells to bortezomib, we are proposing the use of this combination in patients with relapsed/refractory AML or elderly patients who are not candidates for standard induction therapy.
Using the subcutaneous formulation of bortezomib would provide patients with reduced neurotoxicity and easier schedule due to decreased time in the infusion room and it would decrease overall cost of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib + Doxil | Experimental | Drug: Bortezomib, Drug: DoxilBortezomib will be given subcutaneously at 1.5mg/m2 on days 1, 4, 8 and 11 of a 3 week cycle. Doxil will be administered once every three weeks as a single intravenous infusion at a dose of 40 mg/m2 (day 4 of each cycle). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent
- Female subjects must be either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of SQ VELCADE, or agree to completely abstain from heterosexual intercourse.
- Male subjects, even if surgically sterilized must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- Adults (age 18 to 80) with AML, excluding the M3 subtype, that are not likely to respond to conventional therapy
- Bone marrow and peripheral blood studies must be available for confirmation of diagnosis.
Key exclusion criteria (14 listed)
- There is no specific platelet and absolute neutrophil count that will exclude patients from this study given the natural history of AML.
- Patient has greater than or equal to Grade 2 peripheral neuropathy
- Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant. An left ventricular ejection fraction (LVEF) must be > 50
- Patient has hypersensitivity to VELCADE, boron, or mannitol.
- Female subject is pregnant or lactating.
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: VelcadeBortezomib will be given twice a week subcutaneously (under the skin) for two weeks in every 3 week cycle. | Drug | Bortezomib + Doxil |
| DoxilAlso: LipoDox; pegylated liposomal doxorubicinDoxil or LipoDox will also be given through a venous catheter (inside your vein). Doxil or LipoDox will be given over 60 to 90 minutes on Day 4 of every 21-day cycle. | Drug | Bortezomib + Doxil |
Primary outcome
Progression Free Survival
Time frame: Up to 2 years
The time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.
2 secondary outcomes
Overall Survival
Time frame: Up to two years
Toxicity Information Recorded Will Include the Type, Severity, Time of Onset, Time of Resolution, and the Probable Association With the Study Regimen.
Time frame: Up to two years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Joseph Tuscano, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib and Doxil in people with Acute Myelogenous Leukemia, run by Joseph Tuscano 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 11 inclusion and 14 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 24 Feb 2021. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression Free Survival (time frame: Up to 2 years). 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 24 Feb 2021.