- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00936611
LBH589 in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia
Phase II Trial of LBH589 (Panobinostat) in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia
Study Overview
Detailed Description
This phase II study is designed to assess the toxicity profile and the proportion of overall response in patients with relapsed or refractory WM. This will study the effect of single agent LBH589 on response in these patients. Efficacy measures will include both objective clinical measurements and investigator-reported outcomes. Response and time to event analyses will follow the criteria set forth in the International Waldenstrom consortium recommendations. Prior to the start of the study, investigators will assess disease and perform a CT scan of the chest, abdomen and pelvis.
Response will be assessed after 2 cycles. If patients have stable disease or response, then they will continue on therapy until progression or unacceptable toxicity, being assessed every cycle until the sixth cycle and then every 3 months. Patients who show progression after 2 cycles will come off therapy and undergo event monitoring every 3 months. All responses will be assessed by M-protein quantification and immunofixation from serum and IgM monoclonal protein level. In addition, BM biopsies will be done at baseline, at the end of cycle 6 and at the end of all therapy. The protocol was amended because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Colorado
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Denver, Colorado, United States, 80220
- Rocky Mountain Cancer Centers
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female patients aged 18 years or older
- Must have received prior therapy for their WM, any number of prior therapies is allowed
- Must have symptomatic relapsed or refractory WM
- Measurable monoclonal IgM protein in the blood and presence of lymphoplasmacytic cells in the bone marrow during any previous bone marrow
- Laboratory values as described in the protocol
- Clinically euthyroid
- ECOG Performance Status of 2 or less
Exclusion Criteria:
- Prior 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 CTCAE grade 2 or higher
- Impaired cardiac function or clinically significant cardiac diseases
- Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
- Diarrhea > CTCAE grade 1
- Other concurrent severe and/or uncontrolled medical conditions 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
- Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
- Patients who have received chemotherapy or rituximab within 3 weeks or less; or radiation therapy to > 30% of marrow-bearing bone within 2 weeks or less prior to starting study treatment; or who have not yet recovered from side effects of such therapies
- Patients who have received corticosteroids 2 weeks or less prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than than Waldenstrom's Macroglobulinemia
- Patients with active bleeding tendency or receiving any treatment with therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin to maintain line patency is allowed
- Patients who have undergone major surgery 4 weeks or less 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 not using an effective method of birth control
- Male patients whose sexual partners are women of childbearing potential not using effective methods of birth control
- Patients with prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Patients with a 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: LBH589
30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to:
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate
Time Frame: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.
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Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment. CR
VGPR -At least 90% reduction of serum monoclonal IgM concentration on protein electrophoresis. PR
MR
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Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Progression Free Survival
Time Frame: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).
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Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods.
Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.
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Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).
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Median Time to Progression
Time Frame: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).
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Time to progression (TTP) is defined as the time from start of treatment to progression.
Patients who have not progressed are censored at the date the patient is last known to be progression free.
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Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).
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Median Duration of Response
Time Frame: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).
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Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression Patients who have died for any cause or are alive without progression are censored at the date the patient is last know to be progression-free. Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression or death for any cause. Patients who are alive without progression are censored at the date the patient is last know to be progression-free. |
Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).
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Number of Participants With Grade 3 and 4 Treatment-Related Thrombocytopenia
Time Frame: Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.
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Grade 3 thrombocytopenia is defined as having 25,000-50,000 /uL platelets Grade 4 thrombocytopenia is defined as having < 25,000 /uL platelets |
Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.
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Acetylated Histone H3 and Overall Response Association
Time Frame: Bone marrow biopsies were obtained at the start of treatment (baseline) and after the 6th cycle.
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Acetylated-histone-H3 levels were obtained through bone marrow biopsies and measured using established methods.
This analysis aimed to analyze the association between overall response and percent change of acetylated histone h3 in samples using a paired t-test.
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Bone marrow biopsies were obtained at the start of treatment (baseline) and after the 6th cycle.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Irene Ghobrial, MD, Dana-Farber Cancer Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Waldenstrom Macroglobulinemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Panobinostat
Other Study ID Numbers
- 09-071
- CLBH589CUS56T (Other Identifier: Novartis)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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