Relapsed Acute LeukemiaPhase 1/2NCT00410423
Study of VELCADE® With Mitoxantrone and Etoposide for Leukemias
A Phase 1/2 study testing Bortezomib with mitoxantrone, etoposide and cytarabine, Bortezomib 1.0mg/m^2 and Bortezomib 1.3mg/m^2 in people with Relapsed Acute Leukemia and Refractory Acute Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial summary
Based on what is known about it's mechanism of action, bortezomib is presumed to make other chemotherapy drugs work better. This study examines the use of bortezomib in combination with an already effective chemotherapy regimen that is used to treat leukemias that have relapsed or been refractory to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Acute Leukemia, Refractory Acute Leukemia
- What is being tested?
- Bortezomib with mitoxantrone, etoposide and cytarabine, Bortezomib 1.0mg/m^2 and Bortezomib 1.3mg/m^2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Sep 2014
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) will be eligible for the study.
- Patients must have failed initial therapy that may manifest in either of the following ways:
- Demonstration of Primary Refractory Disease (Primary Induction Failure) as evidenced by a mid-cycle bone marrow analysis showing lack of complete tumor clearance (CTC).
- Relapse of initial disease after a period of attaining complete remission.
Show all 22Show fewer
- Patients must be > 18 years of age, with no upper age limit.
- ECOG performance status of 0 or 1.
- Patients have no symptomatic cardiac or pulmonary disease and adequate hepatic and renal function as measured by the following criteria:
- Cardiac: Left ventricular ejection fraction at rest must be >40% (MUGA preferred)
- Hepatic: ALT and AST < 3x the upper limits of normal range as specified by the institution's clinical laboratory.
- Renal: Serum creatinine within the normal range (< 1.4 mg/dL) or if creatinine outside normal range then creatinine clearance > 60 mL/min/m2
- Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) will be eligible for the study.
- Patients must have failed initial therapy that may manifest in either of the following ways:
- Demonstration of Primary Refractory Disease (Primary Induction Failure) as evidenced by a mid-cycle bone marrow analysis showing lack of complete tumor clearance (CTC).
- Relapse of initial disease after a period of attaining complete remission.
- Patients must be > 18 years of age, with no upper age limit.
- ECOG performance status of 0 or 1.
- Patients have no symptomatic cardiac or pulmonary disease and adequate hepatic and renal function as measured by the following criteria:
- Cardiac: Left ventricular ejection fraction at rest must be >40% (MUGA preferred)
- Hepatic: ALT and AST < 3x the upper limits of normal range as specified by the institution's clinical laboratory.
- Renal: Serum creatinine within the normal range (< 1.4 mg/dL) or if creatinine outside normal range then creatinine clearance > 60 mL/min/m2
Who cannot join
- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), 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 has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urinary pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias
Based on what is known about it's mechanism of action, bortezomib is presumed to make other chemotherapy drugs work better. This study examines the use of bortezomib in combination with an already effective chemotherapy regimen that is used to treat leukemias that have relapsed or been refractory to treatment.
Read the detailed description
VELCADE is a drug that blocks growth of cancer cells and helps destroy them. This research will help us to determine if VELCADE when combined with chemotherapy is useful in treating the leukemia with which you have been diagnosed. Your leukemia is a type that did not respond to chemotherapy or has come back after successful therapy.
VELCADE is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma for patients that have received at least one prior therapy. Multiple Myeloma is a type of cancer that develops from blood cells. The dose of the drug being used in this research study is the same as what is used for the treatment of myeloma but the number of injections is less. VELCADE has, however not been approved by the FDA for use in acute leukemia. Mitoxantrone and etoposide, the other two chemotherapy drugs are also used for treating leukemia.
In the first part of the study, we are going to test the safety of VELCADE at different doses when given with mitoxantrone and etoposide. You may be enrolled at any one of three doses. In the second part, we are going to assess the response to the combination of VELCADE and chemotherapy drugs. You will receive VELCADE at the chosen dose based on safety assessment from Phase I. It will be administered as an intravenous (through the vein) injection on day-1 and day-4 of the 5-day schedule. In addition, you will also receive mitoxantrone over 15 minutes and etoposide over 45 minutes from days 1-5. The first 28 days from the beginning of the treatment will be called a treatment cycle.
On day-14 of the treatment cycle, you will have a bone marrow biopsy done to see if all the leukemia cells have disappeared. If there is no evidence of leukemia, then you may receive growth factors to help your marrow recover faster. If there is still presence of leukemia, in the same amount or more, then the treatment will be considered a failure and you will not receive any more of this treatment.
If there is a partial improvement then you will receive additional cycles of VELCADE with chemotherapy as described above until there are no signs of your disease. This is called a complete remission.
Therapy will be withheld at any time if there is concern that you are having side-effects that are not medically acceptable. Once the side-effects have resolved, VELCADE therapy may be re-started at a lower dose.
It is estimated that you may require about two to three cycles of therapy.
- Conditions
- Relapsed Acute Leukemia, Refractory Acute Leukemia
- Being tested
- Bortezomib with mitoxantrone, etoposide and cytarabine, Bortezomib 1.0mg/m^2, Bortezomib 1.3mg/m^2
- Keywords
- Leukemia, Acute Myeloid Leukemia, Acute Lymphoid / Lymphoblastic Leukemia
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bortezomib with mitoxantrone, etoposide and cytarabineDrug
Also called Velcade
All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.
Bortezomib 1.0mg/m^2Drug
Also called Velcade
All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.
Bortezomib 1.3mg/m^2Drug
Also called Velcade
All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib 0.7mg/m^2 | Experimental | Bortezomib in combination with mitoxantrone, etoposide and cytarabine Receives: Drug: Bortezomib with mitoxantrone, etoposide and cytarabine |
| Bortezomib 1.0mg/m^2 | Experimental | Not described Receives: Drug: Bortezomib 1.0mg/m^2 |
| Bortezomib 1.3mg/m^2 | Experimental | Not described Receives: Drug: Bortezomib 1.3mg/m^2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicity in Phase I
Dose limiting toxicity (DLT) is defined as grade-3 toxicity definitely related to bortezomib or grade-4 toxicity probably or definitely related to bortezomib.
Measured: 30-90 days
Complete Response Rate to 1.3mg/m^2 of Bortezomib With Mitoxantrone and Etoposide in Phase II
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions.
The percentage of participants that experienced complete response will be reported.
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2006 (estimated)
- Study startJan 2006
- Primary completionMay 2013
- Study completionSep 2014
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 Relapsed Acute 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Joanne Filicko-O'Hara, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00410423
- Sponsor's protocol ID
- 06U.70
- Other IDs
- 2005-74, JT 1162
- Status last verified
- Apr 2025
- First submitted
- 11 Dec 2006
- Last updated
- 30 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias
- ClinicalTrials.gov ID
- NCT00410423
- Acronym / sponsor ID
- 06U.70
- Conditions
- Relapsed Acute Leukemia, Refractory Acute Leukemia
- Keywords
- Leukemia, Acute Myeloid Leukemia, Acute Lymphoid / Lymphoblastic Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Jan 2006
- Primary completion
- May 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 12 Dec 2006 (estimated)
- Results
- Posted 17 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Based on what is known about it's mechanism of action, bortezomib is presumed to make other chemotherapy drugs work better. This study examines the use of bortezomib in combination with an already effective chemotherapy regimen that is used to treat leukemias that have relapsed or been refractory to treatment.
Detailed description
VELCADE is a drug that blocks growth of cancer cells and helps destroy them. This research will help us to determine if VELCADE when combined with chemotherapy is useful in treating the leukemia with which you have been diagnosed. Your leukemia is a type that did not respond to chemotherapy or has come back after successful therapy.
VELCADE is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma for patients that have received at least one prior therapy. Multiple Myeloma is a type of cancer that develops from blood cells. The dose of the drug being used in this research study is the same as what is used for the treatment of myeloma but the number of injections is less. VELCADE has, however not been approved by the FDA for use in acute leukemia. Mitoxantrone and etoposide, the other two chemotherapy drugs are also used for treating leukemia.
In the first part of the study, we are going to test the safety of VELCADE at different doses when given with mitoxantrone and etoposide. You may be enrolled at any one of three doses. In the second part, we are going to assess the response to the combination of VELCADE and chemotherapy drugs. You will receive VELCADE at the chosen dose based on safety assessment from Phase I. It will be administered as an intravenous (through the vein) injection on day-1 and day-4 of the 5-day schedule. In addition, you will also receive mitoxantrone over 15 minutes and etoposide over 45 minutes from days 1-5. The first 28 days from the beginning of the treatment will be called a treatment cycle.
On day-14 of the treatment cycle, you will have a bone marrow biopsy done to see if all the leukemia cells have disappeared. If there is no evidence of leukemia, then you may receive growth factors to help your marrow recover faster. If there is still presence of leukemia, in the same amount or more, then the treatment will be considered a failure and you will not receive any more of this treatment.
If there is a partial improvement then you will receive additional cycles of VELCADE with chemotherapy as described above until there are no signs of your disease. This is called a complete remission.
Therapy will be withheld at any time if there is concern that you are having side-effects that are not medically acceptable. Once the side-effects have resolved, VELCADE therapy may be re-started at a lower dose.
It is estimated that you may require about two to three cycles of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bortezomib 0.7mg/m^2 | Experimental | Drug: Bortezomib with mitoxantrone, etoposide and cytarabineBortezomib in combination with mitoxantrone, etoposide and cytarabine |
| Bortezomib 1.0mg/m^2 | Experimental | Drug: Bortezomib 1.0mg/m^2 |
| Bortezomib 1.3mg/m^2 | Experimental | Drug: Bortezomib 1.3mg/m^2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) will be eligible for the study.
- Patients must be > 18 years of age, with no upper age limit.
- ECOG performance status of 0 or 1.
Key exclusion criteria (6 listed)
- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), 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 has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urinary pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 14 days before enrollment
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 |
|---|---|---|
| Bortezomib with mitoxantrone, etoposide and cytarabineAlso: VelcadeAll patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital. | Drug | Bortezomib 0.7mg/m^2 |
| Bortezomib 1.0mg/m^2Also: VelcadeAll patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital. | Drug | Bortezomib 1.0mg/m^2 |
| Bortezomib 1.3mg/m^2Also: VelcadeAll patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital. | Drug | Bortezomib 1.3mg/m^2 |
Primary outcome
Number of Participants With Dose Limiting Toxicity in Phase I
Time frame: 30-90 days
Dose limiting toxicity (DLT) is defined as grade-3 toxicity definitely related to bortezomib or grade-4 toxicity probably or definitely related to bortezomib.
Complete Response Rate to 1.3mg/m^2 of Bortezomib With Mitoxantrone and Etoposide in Phase II
Time frame: Up to 7 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. The percentage of participants that experienced complete response will be reported.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Thomas Jefferson University HospitalsLink provided by the sponsor.
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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.
Joanne Filicko-O'Hara, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bortezomib with mitoxantrone, etoposide and cytarabine, Bortezomib 1.0mg/m^2 and Bortezomib 1.3mg/m^2 in people with Relapsed Acute Leukemia and Refractory Acute Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University 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 22 inclusion and 6 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 30 Apr 2025. 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 combined 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.
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 17 Apr 2018). 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?
Number of Participants With Dose Limiting Toxicity in Phase I (time frame: 30-90 days). The study lists 2 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 30 Apr 2025.