LBH589 in Refractory Myelodysplastic Syndromes (MDS)

This study has been terminated.
(Per protocol, the results of a planned interim analysis demonstrated insufficient efficacy and led to early termination of the study.)
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00594230
First received: December 19, 2007
Last updated: October 8, 2015
Last verified: October 2015
  Purpose
This will be a single arm Phase II study.

Condition Intervention Phase
Myelodysplastic Syndromes (MDS)
Drug: Panobinostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of LBH589 in Refractory Myelodysplastic Syndromes (MDS) Patients

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS. [ Time Frame: Every 8 weeks up to 24 months on-study. ] [ Designated as safety issue: No ]
    Overall response rate (ORR) is defined by the modified International Working Group (IWG) Response Criteria for MDS. In the marrow, Complete Response (CR) is <= 5% blasts present with normal maturation of all cell lines. In peripheral blood, CR is defined as hemoglobin >= 11 g/dL, ANC >= 1000/mL, and platelets >= 100,000 with 0% blasts present. Partial Response (PR) is defined the same as CR with blasts decreased by >= 50% and >= 5% blasts in the marrow.


Secondary Outcome Measures:
  • Time to Disease Progression [ Time Frame: Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of disease ] [ Designated as safety issue: No ]

    Time to disease progression is defined as the time between day 1 cycle 1 and time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    NOTE: Study terminated early, no results are available for this endpoint


  • Hematologic Improvement, Including Transfusion Independence [ Time Frame: Every 8 weeks up to 24 months on-study ] [ Designated as safety issue: No ]

    Hematologic measures will include total WBC and platelets

    NOTE: Study terminated early, no results are available for this endpoint


  • Duration of Response [ Time Frame: Every 8 weeks up to 24 months on-study ] [ Designated as safety issue: No ]

    Duration of response is defined as the time from when objective response is realized until time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Objective Response = CR + PR. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

    NOTE: Study terminated early, no results are available for this endpoint


  • Median Time to Treatment Failure [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    Time to treatment failure is defined as measuring the time between cycle 1 day 1 to discontinuation for any reason.

    NOTE: Study terminated early, no results are available for this endpoint


  • Median Overall Survival [ Time Frame: 24 months on-study, patients followed every 3 months in follow-up ] [ Designated as safety issue: No ]

    The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

    NOTE: Study terminated early, no results are available for this endpoint


  • Safety and Tolerability of LBH589 in Patients With Relapsed/Refractory MDS [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    NOTE: Study terminated early, no results are available for this endpoint


Enrollment: 26
Study Start Date: January 2008
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panobinostat 20 mg
Treatment with LBH589 (Panobinostat) 20 mg
Drug: Panobinostat
Panobinostat(20 mg or 30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Other Name: LBH589
Experimental: Panobinostat 30 mg
Treatment with LBH589 (Panobinostat) 30 mg
Drug: Panobinostat
Panobinostat(20 mg or 30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Other Name: LBH589

Detailed Description:
LBH589 (20 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytological documented diagnosis of myelodysplastic syndrome (MDS).
  • Male or female patients aged >= 18 years old.
  • MDS patients who have failed hypomethylating (azacitidine or decitabine) therapy.
  • Patients with 5q-cytogenic abnormalities must also have progressed on or been intolerant to lenalidomide.
  • Patients with up to and including 30% blasts (FAB RAEB-T) will be eligible to enroll.
  • CMML with >= 5% blasts will be eligible to enroll.
  • ECOG PS 0, 1 or 2.
  • Laboratory values must be as follows:

Bilirubin <= 1.5 mg/dL AST/SGOT <= 2.5 x ULN ALT/SGPT Creatinine <= 2.0 mg/dL or 24-hour Creatinine Clearance >= 50 ml/min Albumin >= 3 g/dL Potassium >= lower limit normal (LLN) Phosphorous >= LLN Calcium >= LLN Magnesium >= LLN

  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.
  • Life expectancy >= 12 weeks.

Exclusion Criteria:

  • Prior treatment with an HDAC inhibitor.
  • Prior intensive chemotherapy or high dose ara-C (>= 1 gm/m2)
  • More than one prior single agent chemotherapy regimen. Prior hydroxyurea for cytoreduction will be permitted however.
  • Impaired cardiac function
  • Active CNS disease, including leptomeningeal metastases.
  • Unresolved diarrhea > CTCAE grade 1.
  • Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
  • Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method.
  • Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
  • Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
  • Other concurrent severe, uncontrolled systemic fungal, bacterial, viral or other infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with uncontrolled coagulopathy.
  • Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594230

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
Novartis Pharmaceuticals
Investigators
Study Chair: Ian W. Flinn, M.D. SCRI Development Innovations, LLC
  More Information

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00594230     History of Changes
Other Study ID Numbers: SCRI MDS 07 
Study First Received: December 19, 2007
Results First Received: August 22, 2012
Last Updated: October 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Myelodysplastic Syndromes (MDS)
Refractory
LBH589

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Panobinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 25, 2016