Clinical trial NCT00601718
Conditions: Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Contiguous Stage II Mantle Cell Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Splenic Marginal Zone Lymphoma Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Mantle Cell Lymphoma Stage I Mycosis Fungoides/Sezary Syndrome Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Mycosis Fungoides/Sezary Syndrome Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Mantle Cell Lymphoma Stage III Mycosis Fungoides/Sezary Syndrome Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Waldenström Macroglobulinemia
Sponsor: University of Washington
Start date: 2007-12-01; Completion date: 2010-06-01
Enrollment: 29 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial is studying the side effects and best dose of vorinostat when given together with rituximab, ifosfamide, carboplatin, and etoposide and to see how well they work in treating patients with relapsed or refractory lymphoma or previously untreated T-cell non-Hodgkin lymphoma or mantle cell lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with rituximab and combination chemotherapy may kill more cancer cells

Detailed description:
OBJECTIVES:

I. To determine maximally tolerated dose of vorinostat that can be combined with RICE chemotherapy in patients with relapsed lymphoid malignancies.

II. To determine the safety and toxicity of the above regimen. III. To gain a preliminary assessment of the efficacy of the above regimen. IV. To determine the ability to proceed to peripheral blood stem cell collection following the above regimens (the impact of above regimen on stem cell reserve).

V. To describe vorinostat concentration attained at or near the MTD. VI. To evaluate the change of histone acetylation patterns and pro-apoptotic proteins of primary target (tumor) and non-target peripheral blood mononuclear cells (PBMC) cells following high-dose HDAC inhibition.

VII. To describe the gene expression profile changes of tumor and non-tumor cells following high-dose HDAC inhibition.

OUTLINE: This is a phase I/II dose-escalation study of vorinostat.

Patients receive vorinostat orally (PO) once daily (QD) on days 1-5, ifosfamide IV continuously over 24 hours and carboplatin IV over 1 hour on day 4, and etoposide IV over 1 hour on days 3-5. Patients who are CD20+ also receive rituximab IV once on day 3, 4, or 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.

Arms: arm 1: Patients receive vorinostat PO QD on days 1-5, ifosfamide IV continuously over 24 hours and carboplatin IV over 1 hour on day 4, and etoposide IV over 1 hour on days 3-5. Patients who are CD20+ also receive rituximab IV once on day 3, 4, or 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: vorinostat intervention 2: rituximab intervention 3: ifosfamide intervention 4: carboplatin intervention 5: etoposide intervention 6: pharmacological study intervention 7: laboratory biomarker analysis intervention 8: gene expression analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV intervention 6: Correlative studies intervention 7: Correlative studies intervention 8: Correlative studies

Protocol documents: