Full Text View
Tabular View
No Study Results Posted
Related Studies
Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: July 25, 2008   Last Updated: June 23, 2009   History of Changes
Sponsors and Collaborators: Beckman Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00723203
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: panobinostat
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Hematological response rate (morphologic complete response or partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Assessment of biological correlates [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: April 2008
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00723203

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Bernadette Pulone, RN     800-826-4673        
City of Hope Medical Group Recruiting
Pasadena, California, United States, 91105
Contact: Mark V. McNamara, MD     626-396-2900     mmcnamara@ccsmg.com    
Sponsors and Collaborators
Beckman Research Institute
Investigators
Principal Investigator: Mark H. Kirschbaum, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Comprehensive Cancer Center ( Mark H. Kirschbaum )
Study ID Numbers: CDR0000601203, CHNMC-07174, NOVARTIS-CHNMC-07174
Study First Received: July 25, 2008
Last Updated: June 23, 2009
ClinicalTrials.gov Identifier: NCT00723203     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia

Study placed in the following topic categories:
Philadelphia Chromosome
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Recurrence
Leukemia
Lymphatic Diseases
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Lymphoproliferative Disorders
Lymphoma
Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:
Lymphatic Diseases
Leukemia
Neoplasms
Leukemia, Lymphoid
Immunoproliferative Disorders
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Leukemia, Myeloid
Lymphoproliferative Disorders
Leukemia, Myeloid, Acute

ClinicalTrials.gov processed this record on September 11, 2009