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Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma (ZOLINZA)

Primary Purpose

Mantle Cell Lymphoma

Status
Terminated
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat
Sponsored by
Samsung Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring fludarabine, mitoxantrone, dexamethasone, relapsed or refractory mantle cell lymphoma, FND regimen, vorinostat, autologous stem cell transplantation

Eligibility Criteria

19 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

  1. 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

  2. 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

Sites / Locations

  • Samsung Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vorinostat-FND

Arm Description

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)

Outcomes

Primary Outcome Measures

To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated)
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

Secondary Outcome Measures

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
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

Full Information

First Posted
March 30, 2012
Last Updated
April 13, 2016
Sponsor
Samsung Medical Center
Collaborators
Seok Jin Kim
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1. Study Identification

Unique Protocol Identification Number
NCT01578343
Brief Title
Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma
Acronym
ZOLINZA
Official Title
A Phase II Investigation of Vorinostat in Combination With Intravenous Fludarabine, Mitoxantrone, and Dexamethasone in Patients With Relapsed or Refractory Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Why Stopped
we collected data of a total of 19 patients for an interim analysis. but there are less than 7 responses out of the initial 19 patients.
Study Start Date
June 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
Collaborators
Seok Jin Kim

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma
Keywords
fludarabine, mitoxantrone, dexamethasone, relapsed or refractory mantle cell lymphoma, FND regimen, vorinostat, autologous stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vorinostat-FND
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat
Other Intervention Name(s)
1.Induction treatment (Total 4 cycles) D1-3 Fludarabine D1 Mitoxantrone D1-5 Dexamethasone Vorinostat D1-10 Vorinostat, 2.Consolidation treatment for responders Patients not eligible for transplantation
Intervention Description
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) Consolidation treatment for responders Patients not eligible for transplantation Vorinostat maintenance up to 6 cycles 200mg twice daily for 14 consecutive days from D1 - 14 in a 21 day cycle Delay of the start of the next cycle by up to 7 days will be acceptable. If relapse or progression during maintenance, it will be stopped. Patients eligible for transplantation High-dose chemotherapy followed by autologous stem cell transplantation
Primary Outcome Measure Information:
Title
To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated)
Description
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
Time Frame
A) After 8weeks and 16 weeks of the treatment
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
every 3 months during the 1st two years after enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Won Seog Kim, MD, PhD
Organizational Affiliation
Samsung Meical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
we will share collected data with principal investigator in Korea

Learn more about this trial

Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma

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