LeukemiaPhase 2NCT00723203
Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
A Phase 2 study testing panobinostat, gene expression analysis and reverse transcriptase-polymerase chain reaction in people with Leukemia, run by City of Hope Medical Center at 2 sites in United States.
Trial summary
RATIONALE: Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects of panobinostat and to see how well it works in treating patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- panobinostat, gene expression analysis and reverse transcriptase-polymerase chain reaction
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2008to Sep 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
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia (ALL)
- Relapsed or refractory disease
- Patients with Philadelphia chromosome-positive (Ph+) ALL refractory to BCR/ABL inhibitors are eligible
- Patients who have relapsed after prior autologous or allogenic stem cell transplant are eligible
- No active CNS disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Serum albumin ≥ 3 g/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5.0 times ULN if transaminase elevation is due to leukemic involvement)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
- Potassium ≥ lower limit of normal (LLN)
- Phosphorous ≥ LLN
- Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
- Magnesium ≥ LLN
- Thyroid stimulating hormone and free T4 normal (thyroid hormone replacement therapy allowed)
- LVEF ≥ LLN by MUGA or ECHO
- No impaired cardiac function, including any of the following:
- QTc > 450 msec
- Congenital long QT syndrome
- History of sustained ventricular tachycardia
- History of ventricular fibrillation or torsades de pointes
- Bradycardia (i.e., heart rate < 50 beats per minute)
- Pacemaker allowed provided heart rate ≥ 50 beats per minute
- Myocardial infarction or unstable angina within the past 6 months
- New York Heart Association class III-IV congestive heart failure
- Right bundle branch block and left anterior hemiblock (bifascicular block)
- No uncontrolled hypertension
- No unresolved diarrhea > CTCAE grade 1
- No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception during and for 3 months after completion of study treatment
- No other primary malignancy within the past 5 years, other than curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
- No HIV or hepatitis C positivity
- No other concurrent severe and/or uncontrolled medical condition
- No significant history of non-compliance to medical regimens or inability to give reliable informed consent
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from all prior therapy
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
- More than 4 weeks since prior valproic acid
- No other prior treatment with a histone deacetylase inhibitor
- No concurrent medication that may cause QTc prolongation or induce torsades de pointes
- No concurrent CYP3A4 inhibitors
- No concurrent grapefruit, grapefruit juice, or Seville (sour) oranges
- No concurrent radiotherapy
- No other concurrent anticancer therapy or investigational therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000
South Pasadena Cancer Center
Pasadena, California, 91030
About this study
Official title: A Phase II Study of LBH589, a Novel Histone Deacetylase Inhibitor, in Relapsed and Refractory Adult Patients With Acute Leukemia (AL) or in Newly Diagnosed Patients Over the Age of 60
RATIONALE: Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying the side effects of panobinostat and to see how well it works in treating patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia.
Read the detailed description
OBJECTIVES:
Primary
- To determine the antitumor activity of panobinostat, in terms of objective response rate, time to progression, and survival, in patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia.
- To assess the toxicity of panobinostat in these patients.
Secondary
- To perform correlative laboratory studies to assess changes in various proteins that may be altered by histone deacetylase inhibition therapy.
OUTLINE: Patients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo peripheral blood and bone marrow sample collection at baseline and on day 28 of course 1 for correlative laboratory studies. Samples are analyzed by RT-PCR for reactivation of FANCG, FOXO3A, GADD45A, GADD45B, GADD45G, H2AX, and TP73.
After completion of study treatment, patients are followed for at least 4 weeks.
PROJECTED ACCRUAL: A total of 74 patients (37 with acute myeloid leukemia and 37 with acute lymphoblastic leukemia) will be accrued for this study.
- Conditions
- Leukemia
- Being tested
- panobinostat, gene expression analysis, reverse transcriptase-polymerase chain reaction, laboratory biomarker analysis
- Keywords
- Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia
- Medical subject headings
- Leukemia, 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.
panobinostatDrug
40 mg Monday, Wednesday and Friday of every week in a 28 day cycle
gene expression analysisGenetic
Day 1 and day 28 samples
reverse transcriptase-polymerase chain reactionGenetic
Day 1 and day 28 samples
laboratory biomarker analysisOther
Day 1 and day 28 samples
| Study group | Role | What they receive |
|---|---|---|
| Treatment (panobinostat) | Experimental | Patients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
panobinostat: 40 mg Monday, Wednesday and Friday of every week in a 28 day cycle Receives: Drug: panobinostat; Genetic: gene expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematological Response Rate
Morphologic CR: morphologic leukemia-free state with absolute neutrophil count > 1000/uL and platelet count ≥ 100,000/uL and independent of blood transfusions. Cytogenic CR: morphologic CR along with reversion to a normal karyotype by cytogenetic analysis. Molecular CR: morphologic CR with no residual disease by molecular or flow cytometric detection methods. Morphologic CR with incomplete blood recovery (CRi): morphologic CR except for residual neutropenia (<1000/uL) and/or thrombocytopenia (<1000,000/uL). PR: same hematologic values for a CR but with a decrease of at least 50% in percentage of blasts to a post-treatment value of 5% to 25% in bone marrow aspirate. (If the pre-treatment blast percentage was 50-100% this must decrease to a value between 5-25%. If the pre-treatment blast percentage was 20-49% this must decrease by at least half to a value > 5%.) A value ≤ 5% is also considered a PR if Auer rods are present. Hematological response = morphologic CR+PR.
Measured: Up to 6 cycles of treatment, up to 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2008 (estimated)
- Study startApr 2008
- Primary completionSep 2010
- Study completionSep 2010
Why it stopped: Terminated early due to a lack of efficacy
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 City of Hope Medical CenterThe 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
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Leslie Popplewell, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00723203
- Sponsor's protocol ID
- 07174
- Other IDs
- P30CA033572, CHNMC-07174, NOVARTIS-CHNMC-07174, CDR0000601203
- Status last verified
- Sep 2014
- First submitted
- 25 Jul 2008
- Last updated
- 9 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of LBH589, a Novel Histone Deacetylase Inhibitor, in Relapsed and Refractory Adult Patients With Acute Leukemia (AL) or in Newly Diagnosed Patients Over the Age of 60
- ClinicalTrials.gov ID
- NCT00723203
- Acronym / sponsor ID
- 07174
- Conditions
- Leukemia
- Keywords
- Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated early due to a lack of efficacy
- Enrolment
- 16 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 28 Jul 2008 (estimated)
- Results
- Posted 28 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying the side effects of panobinostat and to see how well it works in treating patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia.
Detailed description
OBJECTIVES:
Primary
- To determine the antitumor activity of panobinostat, in terms of objective response rate, time to progression, and survival, in patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia.
- To assess the toxicity of panobinostat in these patients.
Secondary
- To perform correlative laboratory studies to assess changes in various proteins that may be altered by histone deacetylase inhibition therapy.
OUTLINE: Patients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo peripheral blood and bone marrow sample collection at baseline and on day 28 of course 1 for correlative laboratory studies. Samples are analyzed by RT-PCR for reactivation of FANCG, FOXO3A, GADD45A, GADD45B, GADD45G, H2AX, and TP73.
After completion of study treatment, patients are followed for at least 4 weeks.
PROJECTED ACCRUAL: A total of 74 patients (37 with acute myeloid leukemia and 37 with acute lymphoblastic leukemia) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (panobinostat) | Experimental | Drug: panobinostat, Genetic: gene expression analysis, Genetic: reverse transcriptase-polymerase chain reaction, Other: laboratory biomarker analysisPatients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. panobinostat: 40 mg Monday, Wednesday and Friday of every week in a 28 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| panobinostat40 mg Monday, Wednesday and Friday of every week in a 28 day cycle | Drug | Treatment (panobinostat) |
| gene expression analysisDay 1 and day 28 samples | Genetic | Treatment (panobinostat) |
| reverse transcriptase-polymerase chain reactionDay 1 and day 28 samples | Genetic | Treatment (panobinostat) |
| laboratory biomarker analysisDay 1 and day 28 samples | Other | Treatment (panobinostat) |
Primary outcome
Hematological Response Rate
Time frame: Up to 6 cycles of treatment, up to 24 weeks.
Morphologic CR: morphologic leukemia-free state with absolute neutrophil count > 1000/uL and platelet count ≥ 100,000/uL and independent of blood transfusions. Cytogenic CR: morphologic CR along with reversion to a normal karyotype by cytogenetic analysis. Molecular CR: morphologic CR with no residual disease by molecular or flow cytometric detection methods. Morphologic CR with incomplete blood recovery (CRi): morphologic CR except for residual neutropenia (<1000/uL) and/or thrombocytopenia (<1000,000/uL). PR: same hematologic values for a CR but with a decrease of at least 50% in percentage of blasts to a post-treatment value of 5% to 25% in bone marrow aspirate. (If the pre-treatment blast percentage was 50-100% this must decrease to a value between 5-25%. If the pre-treatment blast percentage was 20-49% this must decrease by at least half to a value > 5%.) A value ≤ 5% is also considered a PR if Auer rods are present. Hematological response = morphologic CR+PR.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2014.
- 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.
Leslie Popplewell, MD principal investigator
City of Hope Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing panobinostat, gene expression analysis and reverse transcriptase-polymerase chain reaction in people with Leukemia, run by City of Hope Medical Center at 2 sites 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?
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 9 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 28 Aug 2014). 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?
Hematological Response Rate (time frame: Up to 6 cycles of treatment, up to 24 weeks.). 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 9 Sep 2014.