LeukemiaPhase 2NCT00818649
Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia
A Phase 2 study testing bortezomib and vorinostat in people with Leukemia and Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndrome
- What is being tested?
- bortezomib and vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to May 2012
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease Specific Criteria: Pathologic Diagnosis must be confirmed by University of Minnesota Hematopathology
- Myelodysplastic Syndrome (MDS): By IPSS Category: INT-2 or High risk, By WHO Classification: RAEB-1 or RAEB-2,By cytogenetics: High Risk Cytogenetic Abnormality Present as defined by the presence Monosomy 7 or complex karyotype. Patients will be eligible after progressing through standard therapy with either Azacitidine or Decitabine. Patients with a history of 5q minus syndrome may be eligible after progressing through treatment with Lenalidomide.
- Acute Myelogenous Leukemia (AML): Histologic subtypes M0,M1,M2,M4,M5,M6,M7 are eligible and must meet one of the three criteria below:
- Refractory Disease/Induction Failure: Failure to achieve initial remission after 2 lines of induction therapy.
- Relapsed Disease
- Newly diagnosed/untreated AML: Patients who are not able to tolerate potentially curative conventional induction chemotherapy due to advanced age, end organ limitations, or performance status limitation will be eligible.
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- Additionally, those that refuse conventional induction therapy will be eligible.
- Patients must have relatively stable bone marrow function during the week prior to enrollment on the study. White Blood cells (WBC) may be controlled with hydrea. Rapid WBC doubling not responsive to control with hydrea would indicate unstable bone marrow function. Ideally WBC should be < 15 X 10^3 /dl at time of study enrollment.
- Age >18 years
- Karnofsky performance status > or = 60%
- Have acceptable organ function as defined within 28 days of enrollment:
- Hematologic: hemoglobin > 8 g/dL, and platelets > 20k. (Patients may receive transfusions of either peripheral red blood cells (PRBC) or platelets to achieve these levels)
- Renal: creatinine < or = 2.0 mg/dL or creatinine clearance > or = 40 ml/min
- Hepatic: ALT, AST < or = 2.5 x upper limit of normal and total bilirubin < or = 1.5 X ULN
- Cardiac: left ventricular ejection fraction > 40% (testing required for all patients. For those with prior cardiac history (defined as prior stent or bypass surgery) a stress test within 1 month prior to proceeding with the study will be required. A cardiology consult will be required for those with prior documented cardiac disease or those with any significant EKG/ECHO abnormalities found on screening tests.
- Patients must not have received treatment for their myeloid disorder within 2 weeks of beginning the trial. Treatments include the use of chemotherapy, hematopoietic growth factors, and biologic therapy such as monoclonal antibodies. The exception is the use of hydroxyurea for patients with an elevated WBC. Given the relatively slower expected clinical response with the study drugs, patients may continue to receive hydroxyurea through the first cycle of therapy.
- Must have recovered from clinically significant toxicities from previous therapies.
- Women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. In addition, women of childbearing potential must have a negative serum pregnancy test b-hCG within 72 hours prior to receiving the first dose of therapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Treatment History Criteria: Patients who have relapsed after allogeneic stem cell transplantation are eligible.
Who cannot join
- Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test within 72 hours prior to study drug administration to rule out pregnancy.
- Grade 2 or greater peripheral neuropathy within 14 days before enrollment
- Active central nervous system (CNS) disease. Patients with any clinical symptoms of active CNS disease must have LP with negative cytology.
- WBC and Peripheral Blast count uncontrolled with hydroxyurea
- Evidence of QT prolongation with QTc interval greater than 0.5 seconds. QTc calculation from the EKG machine will be used for this assessment.
- Clinical evidence of heart failure or history of uncontrolled hypertension. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) 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 has to be documented by the investigator as not medically relevant.
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- Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies
- Patients with prior use of other histone deacetylase inhibitors (excluding valproic acid for seizures with a 30 day wash-out period)
- Known hypersensitivity to Velcade, boron or any of the other agents used in this study
- Patients with a history of deep vein thrombosis/pulmonary embolism (DVT/PE) that has not been adequately treated with systemic anticoagulation or that has been recently diagnosed (within the last 2 months).
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Active HIV or viral hepatitis infection
- Other active and potentially life threatening malignancies excluding localized basal cell or squamous cell skin cancers, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer.
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Phase II Trial of Velcade Plus Vorinostat in the Treatment of High Risk MDS and Relapsed/Refractory AML
RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with vorinostat works in treating patients with high-risk myelodysplastic syndrome or acute myelogenous leukemia.
Read the detailed description
OBJECTIVES:
Primary
- To determine the clinical response to bortezomib and vorinostat in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia, as defined by the International Working Group response criteria.
Secondary
- To characterize the quantitative and qualitative toxicities of this regimen in these patients.
- To assess the effect of this regimen on natural killer (NK) cell function, in terms of activating and inhibitory receptor alterations, target cell ligand and HLA class I modulation, and NK-mediated cell killing.
- To correlate the above changes with clinical response.
OUTLINE: Patients receive bortezomib subcutaneously (SQ) on days 1, 4, 8, and 11 and oral vorinostat once daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response, partial response, or hematologic improvement may receive 3 additional courses of therapy (for a maximum of 6 courses).
Bone marrow and peripheral blood samples are collected at baseline and at the completion of 3 courses of therapy for analysis of target cells (myeloid blasts) (i.e., HLA class I receptor analysis and natural killer [NK] cell receptor ligand analysis) and analysis of activating NK cell receptor alterations and NK-mediated cell killing.
After completion of study treatment, patients are followed periodically for up to 1 year.
- Conditions
- Leukemia, Myelodysplastic Syndrome
- Being tested
- bortezomib, vorinostat
- Keywords
- de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory anemia with excess blasts, adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute minimally differentiated myeloid leukemia (M0), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22)
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Monocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called Velcade
1.3mg/m^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
vorinostatDrug
Also called suberoylanilide hydroxamic acid (SAHA)
400 mg orally (po) every day on days 1-14 of a 21 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Velcade + Vorinostat | Experimental | This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. Receives: Drug: bortezomib; Drug: vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients by Best Clinical Response
Assessed by the International Working Group response criteria: Complete Remission - <5% myeloblasts with normal maturation of all cell lines; Partial Remission - bone marrow blasts decreased by > 50% over pre-treatment but still >5%; and Hematologic Improvement - hemoglobin increase by > 1.5g/dl or decreased transfusions by at least 4/8 week period, platelet absolute increase of >30 X 10^9/L for those starting at >20 X 10^9/L . For those < 20 X 10^9 /L at baseline increase by 100%.
Measured: At Completion of Course 3 (Day 63)
Secondary outcomes (2)
Correlative Laboratory Studies
Analysis of Natural Killer (NK) Cell Activating and Inhibitory Receptor Alterations, NK Cell Receptor Ligand Alterations, HLA Class I Expression on Target Cells (Myeloid Blasts), and NK-mediated Cell Killing
Measured: Pre-Study and After 3 Cycles
Correlation of Cell Alterations With Clinical Response
Analysis of Natural Killer (NK) Cell Activating and Inhibitory Receptor Alterations, NK Cell Receptor Ligand Alterations, HLA Class I Expression on Target Cells (Myeloid Blasts), and NK-mediated Cell Killing
Measured: Pre-Study and After 3 Cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionMay 2012
- Study completionMay 2012
Why it stopped: Met protocol stop rule \[i.e., extreme toxicity\]
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Erica Warlick, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00818649
- Sponsor's protocol ID
- 2008LS044
- Other IDs
- MT2008-06R, 0808M44081, MILLENNIUM-X05269
- Status last verified
- Dec 2017
- First submitted
- 7 Jan 2009
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Velcade Plus Vorinostat in the Treatment of High Risk MDS and Relapsed/Refractory AML
- ClinicalTrials.gov ID
- NCT00818649
- Acronym / sponsor ID
- 2008LS044
- Conditions
- Leukemia, Myelodysplastic Syndrome
- Keywords
- de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory anemia with excess blasts, adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute minimally differentiated myeloid leukemia (M0), adult acute myelomonocytic leukemia (M4)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Met protocol stop rule \[i.e., extreme toxicity\]
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Millennium Pharmaceuticals, Inc.
- Study start
- Jan 2009
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 8 Jan 2009 (estimated)
- Results
- Posted 25 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with vorinostat works in treating patients with high-risk myelodysplastic syndrome or acute myelogenous leukemia.
Detailed description
OBJECTIVES:
Primary
- To determine the clinical response to bortezomib and vorinostat in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia, as defined by the International Working Group response criteria.
Secondary
- To characterize the quantitative and qualitative toxicities of this regimen in these patients.
- To assess the effect of this regimen on natural killer (NK) cell function, in terms of activating and inhibitory receptor alterations, target cell ligand and HLA class I modulation, and NK-mediated cell killing.
- To correlate the above changes with clinical response.
OUTLINE: Patients receive bortezomib subcutaneously (SQ) on days 1, 4, 8, and 11 and oral vorinostat once daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response, partial response, or hematologic improvement may receive 3 additional courses of therapy (for a maximum of 6 courses).
Bone marrow and peripheral blood samples are collected at baseline and at the completion of 3 courses of therapy for analysis of target cells (myeloid blasts) (i.e., HLA class I receptor analysis and natural killer [NK] cell receptor ligand analysis) and analysis of activating NK cell receptor alterations and NK-mediated cell killing.
After completion of study treatment, patients are followed periodically for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Velcade + Vorinostat | Experimental | Drug: bortezomib, Drug: vorinostatThis is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Disease Specific Criteria: Pathologic Diagnosis must be confirmed by University of Minnesota Hematopathology
- Myelodysplastic Syndrome (MDS): By IPSS Category: INT-2 or High risk, By WHO Classification: RAEB-1 or RAEB-2,By cytogenetics: High Risk Cytogenetic Abnormality Present as defined by the presence Monosomy 7 or complex karyotype. Patients will be eligible after progressing through standard therapy with either Azacitidine or Decitabine. Patients with a history of 5q minus syndrome may be eligible after progressing through treatment with Lenalidomide.
- Acute Myelogenous Leukemia (AML): Histologic subtypes M0,M1,M2,M4,M5,M6,M7 are eligible and must meet one of the three criteria below:
- Additionally, those that refuse conventional induction therapy will be eligible.
- Patients must have relatively stable bone marrow function during the week prior to enrollment on the study. White Blood cells (WBC) may be controlled with hydrea. Rapid WBC doubling not responsive to control with hydrea would indicate unstable bone marrow function. Ideally WBC should be < 15 X 10^3 /dl at time of study enrollment.
Key exclusion criteria (13 listed)
- Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test within 72 hours prior to study drug administration to rule out pregnancy.
- Grade 2 or greater peripheral neuropathy within 14 days before enrollment
- Active central nervous system (CNS) disease. Patients with any clinical symptoms of active CNS disease must have LP with negative cytology.
- WBC and Peripheral Blast count uncontrolled with hydroxyurea
- Evidence of QT prolongation with QTc interval greater than 0.5 seconds. QTc calculation from the EKG machine will be used for this assessment.
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: Velcade1.3mg/m^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle | Drug | Velcade + Vorinostat |
| vorinostatAlso: suberoylanilide hydroxamic acid (SAHA)400 mg orally (po) every day on days 1-14 of a 21 day cycle | Drug | Velcade + Vorinostat |
Primary outcome
Number of Patients by Best Clinical Response
Time frame: At Completion of Course 3 (Day 63)
Assessed by the International Working Group response criteria: Complete Remission - <5% myeloblasts with normal maturation of all cell lines; Partial Remission - bone marrow blasts decreased by > 50% over pre-treatment but still >5%; and Hematologic Improvement - hemoglobin increase by > 1.5g/dl or decreased transfusions by at least 4/8 week period, platelet absolute increase of >30 X 10^9/L for those starting at >20 X 10^9/L . For those < 20 X 10^9 /L at baseline increase by 100%.
2 secondary outcomes
Correlative Laboratory Studies
Time frame: Pre-Study and After 3 Cycles
Correlation of Cell Alterations With Clinical Response
Time frame: Pre-Study and After 3 Cycles
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- 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.
Erica Warlick, MD principal investigator
Masonic Cancer Center, University of Minnesota
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 vorinostat in people with Leukemia and Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota 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 20 inclusion and 13 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: stopped early, as of the sponsor's last update on 28 Dec 2017. 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 25 Feb 2013). 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 Patients by Best Clinical Response (time frame: At Completion of Course 3 (Day 63)). 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 28 Dec 2017.