Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromePhase 1NCT00331513
Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes
A Phase 1 study testing vorinostat, idarubicin and laboratory biomarker analysis in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase I trial is studying the side effects and best dose of vorinostat when given together with idarubicin in treating patients with relapsed or refractory leukemia or myelodysplastic syndromes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
- What is being tested?
- vorinostat, idarubicin and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Jan 2010
- 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
- Patients must have histologically or cytologically confirmed relapsed/refractory acute myelogenous leukemia, acute lymphocytic leukemia, myelodysplastic syndrome or blastic phase chronic myelogenous leukemia.
- Patients that have received cumulative doses (or its equivalent to other anthracycline) of more than 290 mg/m^2 of idarubicin will be excluded from the study. No other limitations in terms of number of prior therapies or type of therapies apply to this study.
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Total bilirubin ≤ 2 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine ≤ 2 mg/dL
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- LVEF ≥ 50%
- Not nursing or pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- At least 2 weeks since prior chemotherapy and recovered, unless there is evidence of rapidly progressive disease, at least 24 hours since prior hydroxyurea for rapidly proliferating disease
- At least 2 weeks since prior imatinib mesylate
- At least 2 weeks since prior histone deacetylase inhibitors, including valproic acid
- Maximum cumulative dose of prior idarubicin or equivalent anthracycline drug ≤ 290 mg/m2
- No concurrent epoetin alfa or hematopoietic colony-stimulating factors during the first course of study therapy
- No concurrent prophylactic hematopoietic colony-stimulating factors
- Myelodysplastic syndromes requiring treatment, previously treated with either azacytidine or decitabine, unless it was contraindicated; blastic phase chronic myelogenous leukemia; failed prior imatinib mesylate-based therapy
- Patients with MDS should have received therapy with either 5-azacytidine or 5-aza-2'-deoxycytidine, unless the patient had a contraindication to such therapy, and should require therapy.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients with clinical evidence of CNS disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- No unstable angina pectoris
- Considered ineligible for or refused potentially curative therapy, including allogeneic stem cell transplantation, with or without standard induction therapy
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA) or other agents used in this study
- No ongoing or active infection
- No symptomatic congestive heart failure
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- No cardiac arrhythmia
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
- No concurrent combination antiretroviral therapy for HIV-positive patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Study of Suberoylanilide Hydroxamic Acid (Vorinostat, SAHA) in Combination With Idarubicin in Relapsed or Refractory Leukemia
This randomized phase I trial is studying the side effects and best dose of vorinostat when given together with idarubicin in treating patients with relapsed or refractory leukemia or myelodysplastic syndromes. Drugs used in chemotherapy, such as vorinostat and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with idarubicin may kill more cancer cells.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicities of vorinostat (SAHA) in combination with standard-dose idarubicin in patients with relapsed or refractory acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndromes, acute promyelocytic leukemia, or chronic myelogenous leukemia in blastic phase.
II. Describe the clinical activity of this regimen in these patients. III. Determine the in vivo molecular effects of this regimen, including the effects on DNA topoisomerase IIα mRNA expression and on the induction of γH2AX, histone H3 and H4 acetylation, as well as changes in the gene expression profile.
IV. Determine the pharmacokinetic characteristics of this regimen in these patients.
OUTLINE:
This is a randomized, dose-escalation study of vorinostat (SAHA). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.*
ARM II: Patients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.*
Note: *Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA 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 a dose-limiting toxicity. An additional 10 patients are treated at the MTD.
Patients undergo blood collection and bone marrow biopsies periodically during the study for pharmacologic, biomarker, and genetic studies.
After completion of study treatment, patients are followed at 4 weeks and then periodically thereafter.
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
- Being tested
- vorinostat, idarubicin, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Congenital Abnormalities, Leukemia, Promyelocytic, Acute, Blast Crisis, Myeloproliferative Disorders, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally
idarubicinDrug
Also called 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (vorinostat, idarubicin) | Active comparator | Patients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity. Receives: Drug: vorinostat; Drug: idarubicin; Other: laboratory biomarker analysis; Other: pharmacological study |
| Arm II (vorinostat, idarubicin) | Active comparator | Patients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity. Receives: Drug: vorinostat; Drug: idarubicin; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated dose (MTD) of vorinostat determined by dose-limiting toxicities (DLT) as measured by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.3.0
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2006 (estimated)
- Study startMar 2006
- Primary completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromeStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331513
- Sponsor's protocol ID
- NCI-2009-00094
- Other IDs
- NCI-2009-00094, CDR0000472062, 2005-0031, 6892, U01CA062461
- Status last verified
- Sep 2013
- First submitted
- 30 May 2006
- Last updated
- 30 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Suberoylanilide Hydroxamic Acid (Vorinostat, SAHA) in Combination With Idarubicin in Relapsed or Refractory Leukemia
- ClinicalTrials.gov ID
- NCT00331513
- Acronym / sponsor ID
- NCI-2009-00094
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2006
- Primary completion
- Jan 2010 (actual)
- First posted
- 31 May 2006 (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 randomized phase I trial is studying the side effects and best dose of vorinostat when given together with idarubicin in treating patients with relapsed or refractory leukemia or myelodysplastic syndromes. Drugs used in chemotherapy, such as vorinostat and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with idarubicin may kill more cancer cells.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicities of vorinostat (SAHA) in combination with standard-dose idarubicin in patients with relapsed or refractory acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndromes, acute promyelocytic leukemia, or chronic myelogenous leukemia in blastic phase.
II. Describe the clinical activity of this regimen in these patients. III. Determine the in vivo molecular effects of this regimen, including the effects on DNA topoisomerase IIα mRNA expression and on the induction of γH2AX, histone H3 and H4 acetylation, as well as changes in the gene expression profile.
IV. Determine the pharmacokinetic characteristics of this regimen in these patients.
OUTLINE:
This is a randomized, dose-escalation study of vorinostat (SAHA). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.*
ARM II: Patients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.*
Note: *Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA 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 a dose-limiting toxicity. An additional 10 patients are treated at the MTD.
Patients undergo blood collection and bone marrow biopsies periodically during the study for pharmacologic, biomarker, and genetic studies.
After completion of study treatment, patients are followed at 4 weeks and then periodically thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (vorinostat, idarubicin) | Active comparator | Drug: vorinostat, Drug: idarubicin, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity. |
| Arm II (vorinostat, idarubicin) | Active comparator | Drug: vorinostat, Drug: idarubicin, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have histologically or cytologically confirmed relapsed/refractory acute myelogenous leukemia, acute lymphocytic leukemia, myelodysplastic syndrome or blastic phase chronic myelogenous leukemia.
- Patients that have received cumulative doses (or its equivalent to other anthracycline) of more than 290 mg/m^2 of idarubicin will be excluded from the study. No other limitations in terms of number of prior therapies or type of therapies apply to this study.
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Total bilirubin ≤ 2 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
Key exclusion criteria (12 listed)
- Patients with clinical evidence of CNS disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- No unstable angina pectoris
- Considered ineligible for or refused potentially curative therapy, including allogeneic stem cell transplantation, with or without standard induction therapy
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA) or other agents used in this study
- No ongoing or active infection
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 |
|---|---|---|
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally | Drug | Arm I (vorinostat, idarubicin), Arm II (vorinostat, idarubicin) |
| idarubicinAlso: 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDAGiven IV | Drug | Arm I (vorinostat, idarubicin), Arm II (vorinostat, idarubicin) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (vorinostat, idarubicin), Arm II (vorinostat, idarubicin) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I (vorinostat, idarubicin), Arm II (vorinostat, idarubicin) |
Primary outcome
Maximum-tolerated dose (MTD) of vorinostat determined by dose-limiting toxicities (DLT) as measured by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.3.0
Time frame: 21 days
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 30 Sep 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.
Guillermo Garcia-Manero 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 vorinostat, idarubicin and laboratory biomarker analysis in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, 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 19 inclusion and 12 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 Sep 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 (MTD) of vorinostat determined by dose-limiting toxicities (DLT) as measured by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 (time frame: 21 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 30 Sep 2013.