Oral LBH589 in Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Oral LBH 589, a Novel Histone Deacetylase (HDAC) Inhibitor, in Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma|
- Number of Participants With Desired Response [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]
Investigators intended to assess the rate of overall and complete response by World Health Organization (WHO) classification in patients with relapsed or refractory aggressive mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).
WHO Performance Scale Measures levels of patient capability: 0 Normal activity; 1 Symptoms, but nearly fully ambulatory; 2 Some bed time, but needs to be in bed <50% of normal daytime; 3 Needs to be in bed >50% of normal daytime; 4 Unable to get out of bed.
- Number of Participants With Complete Response (CR) and Partial Response (PR) [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]
Investigators intended to determine the complete and partial responses. Chronic Lymphocytic Leukemia (CLL): Using the NCI criteria - - See definitions in the Detailed Description section for a Complete hematologic Remission, and Partial Response.
Mantle Cell Lymphoma (MCL): Based on the International Workshop to Standardize Response Criteria to NHL (Cheson, JCO 1999) - See definitions in the Detailed Description section for a Complete hematologic Remission, and Partial Response.
- Response Duration [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]Investigators intended to determine the duration of responses.
- Progression Free Survival (PFS) Estimate [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]Investigators intended to estimate the progression free survival time
- Number of Participants With Prolonged Corrected QT (QTc) Interval [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]Investigators intended to monitor the QTc interval in patients receiving oral LBH589
- Number of Participants With Improved Blood and Lymphatic Evaluation Results [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]Investigators intended to evaluate histone acetylation, cytotoxic mixed lymphocyte reaction (MLR) activity, cytokine profiles, and immunologic synapse alterations through peripheral blood correlative studies
- Number of Participants With Adverse Events (AEs) [ Time Frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response ]
Investigators intended to evaluate the safety and tolerability profile of LBH589. Assessments would consist of monitoring and recording all adverse events and serious adverse events, the regular monitoring of hematology, blood chemistry and urine values, vital signs, ECOG performance status, and the regular physical examinations and ECG assessments.
Adverse events will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0. CTCAE v3.0 can be accessed on the National Institute of Health (NIH)/NCI website at http://ctep.cancer.gov/forms/CTCAEv3.pdf.
|Study Start Date:||March 2010|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: Oral drug treatment
LBH589 will be given orally (by mouth), 40 mg once-a-day, 3 times weekly every week on days 1, 3 & 5, then 8, 10 &12, then 15, 17 & 19, then 22, 24 & 26.
The LBH589 capsule(s) should be swallowed by mouth with a glass of water (8 ounces noncarbonated) in the morning. The daily dose of LBH589 should be taken at approximately the same time each day. Patients should avoid eating grapefruit, Seville (sour) orange or drinking grapefruit juice or Seville orange juice during the study.
After 2 cycles of treatment, if patients do not demonstrate a partial response or complete response (all of the tumor is gone) to the therapy they will be removed from the study. If patients do obtain a partial (the tumor(s) have decreased in size or number but there are still tumors present) or complete response then treatment will continue until their disease progresses.
Response Assessment for Mantle Cell Lymphoma
Based on the International Workshop to Standardize Response Criteria to non-hodgkin's lymphoma (NHL) (Cheson, JCO 1999) a complete hematologic remission will be defined as the following:
- Disappearance of all evidence of disease.
- Any positron emission tomography (PET)+ mass prior to therapy must be PET negative after treatment.
- No palpable spleen or liver
- If bone marrow involvement prior to therapy, must document clear bone marrow.
Partial response will be defined as:
- No new areas of disease on clinical exam and regression of previous areas of disease
- Greater than or equal to 50% decrease in the size of prior disease areas per measurement on computed tomography (CT) scan
- No new PET+ areas on PET scan
- No increase in size of liver or spleen
Response Assessment for CLL
Using the National Cancer Institute (NCI) criteria, a complete hematologic remission will be defined as having the following present for 2 or more months:
- Absence of symptoms attributable to CLL
- Normal findings on physical examination
- Absolute lymphocyte count <4000/microL
- Absolute neutrophil count (ANC) >1500/microL
- Platelet count >100,000/microL
- Hemoglobin concentration >11 g/dL (untransfused)
- Bone marrow lymphocytosis <30 percent
- No nodules (lymphoid aggregates) on bone marrow biopsy
A partial response per the NCI criteria will be defined as having the following for 2 or more months:
- A reduction in previously enlarged nodes, spleen, and liver by at · least 50 percent and
- Absolute neutrophil count ≥1500/microL or
- Platelet count ≥100,000/microL or
- Hemoglobin concentration ≥11 g/dL or
- 50 percent improvement over pretherapy reductions in hemoglobin concentration and/or platelet count
Please refer to this study by its ClinicalTrials.gov identifier: NCT01090973
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Celeste Bello, M.D.||H. Lee Moffitt Cancer Center and Research Institute|