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Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

This study has been terminated.
(Terminated early due to a lack of efficacy)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00723203
First Posted: July 28, 2008
Last Update Posted: September 9, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
July 25, 2008
July 28, 2008
June 12, 2014
August 28, 2014
September 9, 2014
April 2008
September 2010   (Final data collection date for primary outcome measure)
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.
Hematological response rate (morphologic complete response or partial response)
Complete list of historical versions of study NCT00723203 on ClinicalTrials.gov Archive Site
Not Provided
  • Overall survival
  • Time to progression
  • Toxicity
  • Assessment of biological correlates
Not Provided
Not Provided
 
Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Leukemia
  • Drug: panobinostat
    40 mg Monday, Wednesday and Friday of every week in a 28 day cycle
  • Genetic: gene expression analysis
    Day 1 and day 28 samples
  • Genetic: reverse transcriptase-polymerase chain reaction
    Day 1 and day 28 samples
  • Other: laboratory biomarker analysis
    Day 1 and day 28 samples
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

Interventions:
  • Drug: panobinostat
  • Genetic: gene expression analysis
  • Genetic: reverse transcriptase-polymerase chain reaction
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
16
September 2010
September 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00723203
07174
P30CA033572 ( U.S. NIH Grant/Contract )
CHNMC-07174
NOVARTIS-CHNMC-07174
CDR0000601203 ( Registry Identifier: NCI PDQ )
Yes
Not Provided
Not Provided
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Leslie Popplewell, MD City of Hope Comprehensive Cancer Center
City of Hope Medical Center
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP