Clinical trial NCT01578343: Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: fludarabine
mitoxantrone
dexamethasone
relapsed or refractory mantle cell lymphoma
FND regimen
vorinostat
autologous stem cell transplantation
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Seok Jin Kim
First posted: 2012-04-16
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: 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

Primary outcomes:
measure: To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated)
timeFrame: A) After 8weeks and 16 weeks of the treatment
Secondary outcomes:
measure: 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
timeFrame: every 3 months during the 1st two years after enrollment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Meical Center
name: Won Seog Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: