- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01578343
Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma (ZOLINZA)
A Phase II Investigation of Vorinostat in Combination With Intravenous Fludarabine, Mitoxantrone, and Dexamethasone in Patients With Relapsed or Refractory Mantle Cell Lymphoma
- Rationale In mantle cell lymphoma, the conventional chemotherapy achieves only temporary responses with a median duration of remissions only from 1 to 2 years. Therefore, mantle cell lymphoma is known as one of the B-cell lymphomas with poor prognosis. Although the treatment outcome of mantle cell lymphoma has been improved since intensive chemotherapy regimens such as HyperCVAD was used, a substantial number of patients are still frequently relapsed after chemotherapy. After relapse, most of them became refractory to various kinds of salvage treatment. That is why the results of most salvage chemotherapy regimens were disappointing. In addition, mantle cell lymphoma generally occurs in elderly people. Thus, intensive salvage chemotherapy may not be feasible for elderly patients. Therefore, an effective, novel combination treatment is urgently needed in relapsed or refractory mantle cell lymphoma patients.
Hypothesis
- Vorinostat will produce synergism with a combination treatment regimen (Fludarabine, mitoxantrone, dexamethasone, FND) without overlapping toxicity
- Vorinostat maintenance treatment will reduce the relapse rate in patients ineligible for autologous stem cell transplantation.
- Purpose A phase II investigation to determin the effectiveness of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphomain patients with relapsed or refractory mantle cell lymphoma.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Objectives 1.1 Primary objective • To determine the efficacy of vorinostat plus FND as an induction treatment
Response rate of vorinostat/FND 1.2 Secondary objective
- Survival outcome
Overall survival and progression-free survival
- To determine the efficacy of vorinostat maintenance treatment
- Relapse rate • Toxicity of vorinostat/FND
- Hematologic and non-hematologic toxicity
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Seoul, Korea, Republic of, 135-710
- Samsung Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion
- Histologically proven mantle cell lymphoma
Adequate organ function as defined by the following criteria:
- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy
- Total serum bilirubin ≤1.5 x ULN
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100,000/µL
- Hemoglobin ≥9.0 g/dL (may be transfused or erythropoietin treated)
- Serum calcium ≤12.0 mg/dL
- Serum creatinine ≤1.5 x ULN
- Normal potassium and magnesium at baseline
- All patients should be relapsed or refractory patients after previous treatments including chemotherapy .
At least one measurable lesion (lymph node or tumor mass)
- The size of lesion must be > 1.0cm in the greatest transverse diameter
- ECOG PS 0-2
- Serum HCG test: negative if a patient is female eligible for pregnancy
Exclusion
- Major surgery or radiation therapy within 4 weeks of starting the study treatment.
- History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease or secondary CNS involvement on CT or MRI scan.
- Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2.
- Pregnancy or breastfeeding.
- Patients with HIV positive
- Patients with HBs antigen positive
- Patients with anti-HCV positive
- History of the use of another HDAC inhibitor: e.g. valproic acid
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Vorinostat-FND
Vorinostat-fludarabine, mitoxantrone, dexamethasone Induction treatment (Total 4 cycles) FND D1-3 Fludarabine 25mg/m2 + NS 100mL iv over 30 min D1 Mitoxantrone 10mg/m2 + NS 100mL iv over 30 min D1-5 Dexamethasone 20mg IV or PO every 4 weeks Vorinostat D1-10 Vorinostat 200mg once daily PO (When vorinostat is concurrently administered with FND regimen, vorinostat will be administered 3 hours before chemotherapy)
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated)
Time Frame: A) After 8weeks and 16 weeks of the treatment
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B) Response criteria 1) Complete response (CR): Disappearance of all detectable clinical and radiographic evidence of disease 2) Partial response (PR): ≥50% decrease in sum of product diameter (SPD) of 6 nodes/nodal masses 3) Stable disease (SD): Disease status is less than PR, but is not PD 4) Progressive disease (PD): Appearance of any new lesions |
A) After 8weeks and 16 weeks of the treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To determine the efficacy of vorinostat maintenance treatment, survival outcome and toxicity of vorinostat/FND measured by CT or MRI scan, CTCAE ver 4.0
Time Frame: every 3 months during the 1st two years after enrollment
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A) Disease status evaluation every 3 months during the 1st two years after enrollment B) Monitoring survival status during the five years after enrollment C) Toxicity evaluation
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every 3 months during the 1st two years after enrollment
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Won Seog Kim, MD, PhD, Samsung Meical Center
Study record dates
Study Major Dates
Study Start
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 (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Mantle-Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Histone Deacetylase Inhibitors
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Fludarabine
- Fludarabine phosphate
- Mitoxantrone
- Vorinostat
Other Study ID Numbers
- SMC2011-11-102-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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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