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

This study is not yet open for participant recruitment.
Verified December 2012 by Samsung Medical Center
Sponsor:
Information provided by (Responsible Party):
Won Seog Kim, Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01578343
First received: March 30, 2012
Last updated: December 30, 2012
Last verified: December 2012
History of Changes
  Purpose
  1. 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.

  2. 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.
  3. 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.

Condition Intervention Phase
Mantle Cell Lymphoma
 Drug: Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: every 3 months during the 1st two years after enrollment ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 48
Study Start Date: January 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
 Drug: Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat
  1. 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)

  2. 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
Other Names:
  • 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

Detailed Description:

  1. 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
  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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 Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01578343

Contacts
Contact: Won Seog Kim, MD, PhD 82-2-3410-6548 wskimsmc@skku.edu
Contact: Seok Jin Kim, MD, PhD 82-2-3410-1766 kstwoh@skku.edu

Locations
Korea, Republic of
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of, 135-710
Principal Investigator: Won Seog Kim, MD, PhD            
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: Won Seog Kim, MD, PhD Samsung Meical Center
  More Information

No publications provided

Responsible Party: Won Seog Kim, Associate professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01578343     History of Changes
Other Study ID Numbers: SMC2011-11-102-001
Study First Received: March 30, 2012
Last Updated: December 30, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Samsung Medical Center:
fludarabine
mitoxantrone
dexamethasone
relapsed or refractory mantle cell lymphoma
 FND regimen
vorinostat
autologous stem cell transplantation

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Fludarabine
Fludarabine monophosphate
Vorinostat
 Mitoxantrone
BB 1101
Vidarabine
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on May 21, 2013