Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma

NCT01578343 | Terminated Phase 2

• 1 other identifier: SMC2011-11-102-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

• 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.

Conditions

Mantle Cell Lymphoma

Keywords

fludarabine; mitoxantrone; dexamethasone; relapsed or refractory mantle cell lymphoma; FND regimen; vorinostat; autologous stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• 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

  A) After 8weeks and 16 weeks of the treatment

Secondary Outcomes (1)

• 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

  every 3 months during the 1st two years after enrollment

Study Arms (1)

Vorinostat-FND

EXPERIMENTAL

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

Interventions

Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat DRUG

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

Also known as: 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

Vorinostat-FND

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Samsung Medical Center: lead
• Seok Jin Kim: collaborator

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Recurrence

Interventions

fludarabine; Mitoxantrone; Dexamethasone; Vorinostat; Transplantation

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Surgical Procedures, Operative

Study Officials

• Won Seog Kim, MD, PhD

  Samsung Meical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: April 16, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: February 1, 2016
• Last Updated: April 15, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share

Locations

KR (1)