Clinical trial NCT00764517
Conditions: Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Indolent Adult Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma
Sponsor: OHSU Knight Cancer Institute
Start date: 2008-08-01; Completion date: 2017-03-01
Enrollment: 57 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well giving vorinostat, cladribine, and rituximab together works in treating patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or B cell non-Hodgkin's lymphoma (NHL) that has returned after a period of improvement. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving vorinostat together with cladribine and rituximab may kill more cancer cells.

Detailed description:
PRIMARY OBJECTIVES:

I. Determine objective response rates of the SCR regimen (vorinostat, cladribine, and rituximab) in B-cell malignancies.

II. Determine the tolerability and toxicities of the SCR regimen.

SECONDARY OBJECTIVES:

I. Evaluate progression free survival in patients treated with SCR. II. Estimate event free survival for patients treated with SCR. III. Determine the contribution (if any) of deoxyribonucleic acid (DNA) methylation/histone deacetylation to disease progression and/or response to SCR combination chemotherapy.

IV. Perform scientific correlates to determine if SCR treatment a) is associated with global and gene specific changes in transcription of messenger ribonucleic acid (mRNA)s and micro ribonucleic acid (MiRNA)s b) is acting as an inhibitor of DNA methylation c) is activating or silencing specific genes or miRNAs.

OUTLINE:

Patients receive vorinostat orally (PO) on days 1-14, cladribine intravenously (IV) over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years and then every 6 months thereafter.

Arms: arm 1: Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\].

Patients receive vorinostat PO on days 1-14, cladribine IV over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. arm 2: Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\].

Patients receive vorinostat PO on days 1-14, cladribine IV over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Cladribine intervention 2: Laboratory Biomarker Analysis intervention 3: Rituximab intervention 4: Vorinostat
Intervention descriptions: intervention 1: Given IV intervention 2: Correlative studies intervention 3: Given IV intervention 4: Given PO

Protocol documents: