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Study of Oral LBH589 in Adult Patients With Refractory Cutaneous T-Cell Lymphoma

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.
 
ClinicalTrials.gov Identifier: NCT00425555
Recruitment Status : Completed
First Posted : January 23, 2007
Results First Posted : August 16, 2021
Last Update Posted : August 20, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study will evaluate the safety and efficacy of LBH489B in adult patients with refractory Cutaneous T-Cell Lymphoma.

Condition or disease Intervention/treatment Phase
Cutaneous T-Cell Lymphoma Drug: Panobinostat Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 139 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Oral LBH589 in Adult Patients With Refractory Cutaneous T-Cell Lymphoma
Study Start Date : January 2007
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013


Arm Intervention/treatment
Experimental: Previously treated with oral bexarotene
Participants received Panobinostat 20 milligrams per day (mg/day) capsule orally, once a day (OD) on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5).
Drug: Panobinostat
Other Name: LBH589

Experimental: No prior oral bexarotene treatment
Participants received Panobinostat 20 milligrams per day (mg/day) capsule orally, once a day (OD) on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5).
Drug: Panobinostat
Other Name: LBH589




Primary Outcome Measures :
  1. Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT) [ Time Frame: Baseline up to 6 Months of Follow up ]

    Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL (Olsen et al 2007).

    Responses in the skin based on SWAT are defined as:

    • Complete Response (CR): no evidence of skin disease
    • Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline
    • Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score
    • Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline.


Secondary Outcome Measures :
  1. The Overall Response Rate Using mSWAT Skin Score [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    Estimate of the response rate of participants with resistant cutaneous T-cell lymphoma (CTCL) treated with Panobinostat using the mSWAT skin scores and 95% CI will be analyzed.

  2. Time to Response for Responders [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    Time to response were summarized. A Kaplan-Meier analysis of time to progression was performed, including estimation and 95% confidence interval of the median time to progression and progression-free survival.

  3. Duration of Response (DOS) [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    Duration of response and time to response were summarized. A Kaplan-Meier analysis of time to progression was performed, including estimation and 95% confidence interval of the median time to progression and progression-free survival.

  4. Progression-free Survival (PFS) [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    PFS is defined as time from first dose of study treatment to progression or death due to any cause, based on modified European Society for Bone and Marrow Transplantation (EBMT) criteria per Investigator's assessment

  5. Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    Skin index measurement (Skindex-29) was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the "Dermatology Survey" page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess emotions scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed.

  6. Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    Skindex-29 was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the "Dermatology Survey" page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess functioning scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed.

  7. Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 [ Time Frame: Baseline up to Cycle 12, an average of 12 months ]
    Skindex-29 was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the "Dermatology Survey" page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess physical symptoms scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed.

  8. Maximum Plasma Concentration (Cmax) of Panobinostat [ Time Frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 ]
    Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Cmax will be missing for that subject. Cmax will be reported in units of ng/mL.

  9. Time to Peak Concentration (Tmax) of Panobinostat [ Time Frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 ]
    Tmax is defined as the time at which the Cmax occurs. It will be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable Cmax in the subject's PK profile, then Tmax will be missing for that subject. Tmax will be reported in units of h.

  10. Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat [ Time Frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 ]
    AUC is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours. The area under the plasma concentration-time curve from time zero to 48 hours. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time.

  11. Time of Clast (Tlast) of Panobinostat [ Time Frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 ]
    Time of Clast (Tlast) will be obtained from the Tlast parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Tlast will be missing for that participants. Tlast will be reported in units of h.

  12. Last Observed Plasma Concentration (Clast) of Panobinostat [ Time Frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 ]
    Clast is defined as the Last observed (quantifiable) plasma concentration (Clast), in units of ng/mL. Blood samples were collected to assess Clast.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Written informed consent obtained prior to any screening procedures
  2. Age ≥ 18 years old
  3. Patients with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome. Patients with SS who have bone marrow involvement are also eligible.
  4. Patients must have received at least two prior treatment regimens at least one of which was a systemic therapy regimen. Systemic regimens include oral bexarotene, PUVA, photophoresis, oral corticosteroids, total skin electron bean therapy, chemotherapy such as methotrexate, and interferon. Topical steroids alone are not considered as a treatment regimen.
  5. Patients must have had disease progression on or following their most recent treatment regimen or an inadequate response to their most recent treatment regimen.
  6. Patients will be accrued to one of two groups: Patients previously treated with oral bexarotene and patients who have not had prior oral bexarotene treatment.

Exclusion criteria:

  1. Prior treatment with an HDAC inhibitor.
  2. Patients with visceral disease including CNS involvement (i.e. stage IVB CTCL). Note; Patients with SS who have bone marrow involvement are eligible.
  3. Impaired cardiac function
  4. Concomitant use of drugs with a risk of causing torsades de pointes
  5. Patients who have received chemotherapy or any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  6. Less than 3 months since prior electron beam therapy
  7. Female patients who are pregnant or breast feeding, or patients of reproductive potential not using an effective method of birth control, and male patients whose sexual partners are women of childbearing potential not using effective birth control
  8. Uncontrolled hypertension
  9. Concomitant use of any anti-cancer therapy or radiation therapy. Low potency topical steroid use is permitted. Topical bexarotene use is prohibited during the trial
  10. Concomitant use of CYP3A4/5 inhibitors.
  11. Patients with unresolved diarrhea > CTCAE grade 1
  12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
  13. Other concurrent severe and/or uncontrolled medical conditions
  14. Patients who would need to receive valproic acid for any reason during the study or ≤ 5 days prior to starting study drug.

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00425555


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications of Results:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00425555    
Other Study ID Numbers: CLBH589B2201
2006-000880-27 ( EudraCT Number )
First Posted: January 23, 2007    Key Record Dates
Results First Posted: August 16, 2021
Last Update Posted: August 20, 2021
Last Verified: August 2021
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Cutaneous T-Cell Lymphoma, adults
Mycosis Fungoides
Sézary Syndrome
CTCL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Panobinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action