Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
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.
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Hematological Response Rate [ Time Frame: Up to 6 cycles of treatment, up to 24 weeks. ] [ Designated as safety issue: No ]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.
|Study Start Date:||April 2008|
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (panobinostat)
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
40 mg Monday, Wednesday and Friday of every week in a 28 day cycleGenetic: gene expression analysis
Day 1 and day 28 samplesGenetic: reverse transcriptase-polymerase chain reaction
Day 1 and day 28 samplesOther: laboratory biomarker analysis
Day 1 and day 28 samples
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00723203
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|South Pasadena Cancer Center|
|Pasadena, California, United States, 91030|
|Principal Investigator:||Leslie Popplewell, MD||Beckman Research Institute|