Non-Hodgkin's LymphomaPhase 2NCT01090973
Oral LBH589 in Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)
A Phase 2 study testing LBH589 in people with Non-Hodgkin's Lymphoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of the study is to find out the effects and the safety of an investigational study drug called LBH589 when given to people with relapsed or refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma
- What is being tested?
- LBH589
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Patients must meet the following laboratory criteria (unless dysfunction is due to organ infiltration by lymphoma):
- ANC ≥ 1.5 x 10^9/L
- Hemoglobin ≥ 9 g/dl
- Platelets ≥ 75 x 10^9/L
- Calculated CrCl ≥50 mL/min (MDRD Formula)
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- Total serum calcium ≥ LLN
- Total serum magnesium ≥ LLN
- Aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
- Serum bilirubin ≤1.5 x ULN
- Serum potassium ≥ LLN
- Thyroid stimulating hormone (TSH) ≥ lower limit of normal (LLN) and free T4 within normal limits. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
- Baseline multiple uptake gate acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Documented MCL by biopsy or CLL by biopsy or flow cytometry.
- Relapsed or refractory disease despite 1 or more lines of therapy.
Who cannot join
- Prior histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
- Peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
- Patients with congenital long QT syndrome
- History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Sponsor prior to enrollment)
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- History of ventricular fibrillation or torsade de pointes
- Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
- Screening 12 lead electrocardiogram (ECG) with a QTc > 450 msec
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
- Other clinically significant heart disease (e.g., congestive heart failure (CHF) New York Heart Association (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LBH589
- Patients with diarrhea > CTCAE grade 1
- Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
- Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
- Have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (which ever is longer) and who have not recovered from side effects of those therapies.
- Have received either immunotherapy within < 8 weeks; chemotherapy within < 4 weeks; or radiation therapy to > 30% of marrow-bearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
- Have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). WOCBP must have a negative serum pregnancy test within 24 hours of receiving the first dose of study medication.
- Male patients whose sexual partners are WOCBP not using effective birth control
- Prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
- Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.
- Have not received prior therapy for aggressive MCL or CLL.
- No documentation of disease refractoriness (i.e. progression of disease despite current therapy or recurrence within 3 months of last treatment) or relapse despite prior therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
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
The purpose of the study is to find out the effects and the safety of an investigational study drug called LBH589 when given to people with relapsed or refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL).
Read the detailed description
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
- Conditions
- Non-Hodgkin's Lymphoma
- Being tested
- LBH589
- Keywords
- relapsed, refractory, CLL, chronic lymphocytic leukemia, MCL, mantle cell lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LBH589Drug
Also called panobinostat, HDAC Inhibitor
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.
| Study group | Role | What they receive |
|---|---|---|
| Oral drug treatment | Experimental | 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. Receives: Drug: LBH589 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Desired 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.
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Secondary outcomes (6)
Number of Participants With Complete Response (CR) and Partial Response (PR)
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.
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Response Duration
Investigators intended to determine the duration of responses.
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Progression Free Survival (PFS) Estimate
Investigators intended to estimate the progression free survival time
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Number of Participants With Prolonged Corrected QT (QTc) Interval
Investigators intended to monitor the QTc interval in patients receiving oral LBH589
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Number of Participants With Improved Blood and Lymphatic Evaluation Results
Investigators intended to evaluate histone acetylation, cytotoxic mixed lymphocyte reaction (MLR) activity, cytokine profiles, and immunologic synapse alterations through peripheral blood correlative studies
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Number of Participants With Adverse Events (AEs)
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.
Measured: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: Pharmaceutical company request.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Celeste Bello, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01090973
- Sponsor's protocol ID
- MCC-15971
- Other IDs
- IRB # Pro00000102, CLBH589B25T
- Status last verified
- Jan 2012
- First submitted
- 18 Mar 2010
- Last updated
- 16 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01090973
- Acronym / sponsor ID
- MCC-15971
- Conditions
- Non-Hodgkin's Lymphoma
- Keywords
- relapsed, refractory, CLL, chronic lymphocytic leukemia, MCL, mantle cell lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Pharmaceutical company request.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Mar 2010
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 23 Mar 2010 (estimated)
- Results
- Posted 28 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to find out the effects and the safety of an investigational study drug called LBH589 when given to people with relapsed or refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL).
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral drug treatment | Experimental | Drug: LBH589LBH589 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Patients must meet the following laboratory criteria (unless dysfunction is due to organ infiltration by lymphoma):
- Baseline multiple uptake gate acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Documented MCL by biopsy or CLL by biopsy or flow cytometry.
Key exclusion criteria (26 listed)
- Prior histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
- Peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LBH589
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LBH589Also: panobinostat, HDAC InhibitorThe 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. | Drug | Oral drug treatment |
Primary outcome
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.
6 secondary outcomes
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
Response Duration
Time frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Progression Free Survival (PFS) Estimate
Time frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Number of Participants With Prolonged Corrected QT (QTc) Interval
Time frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
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
Number of Participants With Adverse Events (AEs)
Time frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Celeste Bello, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LBH589 in people with Non-Hodgkin's Lymphoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Desired Response (time frame: 8 weeks (2 cycles) unless treatment continues due to partial or complete response). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2013.