Adult Acute Erythroid Leukemia (M6)Phase 2NCT00305773
Vorinostat in Treating Patients With Acute Myeloid Leukemia
A Phase 2 study testing vorinostat in people with Adult Acute Erythroid Leukemia (M6) and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving the drug in different ways may kill more cancer cells. This randomized phase II trial is studying two different schedules of vorinostat to see how well they work in treating patients with acute myeloid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
- What is being tested?
- vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Jan 2010
- 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
- Diagnosis of acute myeloid leukemia (AML), meeting 1 of the following criteria:
- Relapsed AML in the following categories:
- Good-risk cytogenetics [inv(16), t (8;21)] in second relapse or in first relapse following a remission of < 12 months
- Acute promyelocytic leukemia (M3) in second relapse or greater AND must have relapsed following both tretinoin-anthracycline-based therapy and arsenic trioxide-based therapy
- All other relapsed patients are eligible
- Untreated AML in the following categories:
Show all 35Show fewer
- At least 65 years of age
- Myelodysplastic syndromes-AML (AML with trilineage dysplasia)
- AML with del5Q or monosomy 5, monosomy 7, or complex cytogenetics (≥ 3 cytogenetic abnormalities)
- Refused or ineligible for potentially curative options such as allogeneic stem cell transplantation
- No clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
- ECOG performance status (PS) 0-2 or Karnofsky PS ≥ 60%
- Life expectancy ≥ 3 months
- Bilirubin normal unless attributed to hemolysis or Gilbert's disease in the opinion of the investigator
- AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
- No uncontrolled intercurrent illness, including any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would limit compliance with study requirements
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No known HIV positivity
- More than 4 weeks since prior radiotherapy
- More than 2 weeks since prior valproic acid
- More than 3 weeks since other prior treatment for AML, including hematopoietic growth factors
- Hydroxyurea for WBC > 30,000/mm^3 allowed
- Recovered from prior therapy
- No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), epoetin alfa, or darbepoetin alfa
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies for this cancer
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)
Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving the drug in different ways may kill more cancer cells. This randomized phase II trial is studying two different schedules of vorinostat to see how well they work in treating patients with acute myeloid leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the toxicity and the proportion of complete remissions associated with two different treatment schedules of vorinostat (SAHA) in patients with acute myeloid leukemia.
SECONDARY OBJECTIVES:
- Determine the toxic effects of SAHA in this study population. II. Examine for preliminary evidence of re-expression of silenced genes in leukemic blasts in response to SAHA.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease status (relapsed vs untreated). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 2 years.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
- Conditions
- Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2)
- Being tested
- vorinostat
- Medical subject headings
- Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Promyelocytic, 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 once daily
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally three times daily
| Study group | Role | What they receive |
|---|---|---|
| Arm I (once daily vorinostat) | Experimental | Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: vorinostat |
| Arm II (thrice daily vorinostat) | Experimental | Patients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Complete Response (CR) Rate
The confirmed complete response rate was estimated by the number of participants with CR divided by the total number of evaluable participants.
According to the International Working Group (IWG) Criteria for response in AML, to be considered a CR, the following must be met for at least 4 weeks: ANC > 1500/mL, platelets > 100000/mL, no circulating blasts, bone marrow cellularity >20% (biopsy), trilineage maturation, < 5% bone marrow blasts, no auer rods and no extramedullary disease.
Measured: Up to 2 years
Secondary outcomes (3)
Time to Progression (TTP)
Time to Progression (TTP) for each patient will be calculated as the number of days from date of registration to either date when disease progression was documented or date of last evaluation without disease progression. The TTP distribution will be estimated using the method of Kaplan-Meier
Measured: Duration of study (up to 2 years)
Overall Survival (OS)
Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Measured: Duration of study (up to 2 years)
Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
Description of Grades:
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death
Measured: Duration of study (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2006 (estimated)
- Study startJan 2006
- Primary completionMay 2009
- Study completionJan 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Acute Erythroid Leukemia (M6)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Steven Gore, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00305773
- Sponsor's protocol ID
- NCI-2012-01470
- Other IDs
- NCI-2012-01470, CDR0000465213, JHOC-J0557, MAYO-MC0483, JHOC-J0550, NCI-6882, MC0483, 6882
- Status last verified
- Dec 2012
- First submitted
- 21 Mar 2006
- Last updated
- 19 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Schaefer EW, Loaiza-Bonilla A, Juckett M, DiPersio JF, Roy V, Slack J, Wu W, Laumann K, Espinoza-Delgado I, Gore SD; Mayo P2C Phase II Consortium. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica. 2009 Oct;94(10):1375-82. doi: 10.3324/haematol.2009.009217.
PubMed 19794082
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT00305773
- Acronym / sponsor ID
- NCI-2012-01470
- Conditions
- Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2006
- Primary completion
- May 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 22 Mar 2006 (estimated)
- Results
- Posted 16 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving the drug in different ways may kill more cancer cells. This randomized phase II trial is studying two different schedules of vorinostat to see how well they work in treating patients with acute myeloid leukemia.
Detailed description
PRIMARY OBJECTIVES:
- Determine the toxicity and the proportion of complete remissions associated with two different treatment schedules of vorinostat (SAHA) in patients with acute myeloid leukemia.
SECONDARY OBJECTIVES:
- Determine the toxic effects of SAHA in this study population. II. Examine for preliminary evidence of re-expression of silenced genes in leukemic blasts in response to SAHA.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease status (relapsed vs untreated). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 2 years.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (once daily vorinostat) | Experimental | Drug: vorinostatPatients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. |
| Arm II (thrice daily vorinostat) | Experimental | Drug: vorinostatPatients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses 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 (35 listed)
- Diagnosis of acute myeloid leukemia (AML), meeting 1 of the following criteria:
- Refused or ineligible for potentially curative options such as allogeneic stem cell transplantation
- No clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
- ECOG performance status (PS) 0-2 or Karnofsky PS ≥ 60%
- Life expectancy ≥ 3 months
Key exclusion criteria (0 listed)
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 once daily | Drug | Arm I (once daily vorinostat) |
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally three times daily | Drug | Arm II (thrice daily vorinostat) |
Primary outcome
Confirmed Complete Response (CR) Rate
Time frame: Up to 2 years
The confirmed complete response rate was estimated by the number of participants with CR divided by the total number of evaluable participants. According to the International Working Group (IWG) Criteria for response in AML, to be considered a CR, the following must be met for at least 4 weeks: ANC > 1500/mL, platelets > 100000/mL, no circulating blasts, bone marrow cellularity >20% (biopsy), trilineage maturation, < 5% bone marrow blasts, no auer rods and no extramedullary disease.
3 secondary outcomes
Time to Progression (TTP)
Time frame: Duration of study (up to 2 years)
Overall Survival (OS)
Time frame: Duration of study (up to 2 years)
Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events
Time frame: Duration of study (up to 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19794082Schaefer EW, Loaiza-Bonilla A, Juckett M, DiPersio JF, Roy V, Slack J, Wu W, Laumann K, Espinoza-Delgado I, Gore SD; Mayo P2C Phase II Consortium. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica. 2009 Oct;94(10):1375-82. doi: 10.3324/haematol.2009.009217.
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.
Steven Gore principal investigator
Mayo Clinic
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 vorinostat in people with Adult Acute Erythroid Leukemia (M6) and Adult Acute Megakaryoblastic Leukemia (M7), 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 35 inclusion and 0 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 19 May 2014. 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 16 May 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?
Confirmed Complete Response (CR) Rate (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?
On the ClinicalTrials.gov record for NCT00305773, which also lists 1 linked publication.
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 19 May 2014.