Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

All Drugs and Chemicals

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

The purpose of this study is to provide patients who have relapsed or refractory Mantle Cell Lymphoma (MCL) with early access to an investigational medication called ibrutinib (PCI-32765) and to collect safety information about the drug.

An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

An Open-Label Treatment Use Protocol for Ibrutinib (PCI-32765) in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

Pharmacyclics LLC.

Janssen Biotech, Inc.

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Analgesics

Anti-Infective Agents

Dexamethasone

Mitoxantrone

Fludarabine

Fludarabine phosphate

Dexamethasone acetate

Vorinostat

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Histone Deacetylase Inhibitors

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)

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

Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat

Won Seog Kim, MD, PhD

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.

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

Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma

A Phase II Investigation of Vorinostat in Combination With Intravenous Fludarabine, Mitoxantrone, and Dexamethasone in Patients With Relapsed or Refractory Mantle Cell Lymphoma

we will share collected data with principal investigator in Korea

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) 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

Seok Jin Kim

Samsung Medical Center

Associate professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma	NCT01833039	Relapsed or Ref...	Ibrutinib	18 Years -	Janssen Biotech, Inc.
Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma	NCT01578343	Mantle Cell Lym...	Fludarabine, Mi...	19 Years - 75 Years	Samsung Medical Center
An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma	NCT01833039	Relapsed or Ref...	Ibrutinib	18 Years -	Janssen Biotech, Inc.
Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma	NCT01578343	Mantle Cell Lym...	Fludarabine, Mi...	19 Years - 75 Years	Samsung Medical Center

Spots Global Cancer Trial Database for relapsed or refractory mantle cell lymphoma